DOCSLIB.ORG

Regulatory B Cells in Autoimmune Diseases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Regulatory B Cells in Autoimmune Diseases Cellular & Molecular Immunology (2013) 10, 122–132 ß 2013 CSI and USTC. All rights reserved 1672-7681/13 $32.00 www.nature.com/cmi REVIEW Regulatory B cells in autoimmune diseases Min Yang1,3,KeRui2,3, Shengjun Wang2 and Liwei Lu1 B cells are generally considered to be positive regulators of the immune response because of their capability to produce antibodies, including autoantibodies. The production of antibodies facilitates optimal CD41 T-cell activation because B cells serve as antigen-presenting cells and exert other modulatory functions in immune responses. However, certain B cells can also negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact. These types of B cells are defined as regulatory B (Breg) cells. The regulatory function of Breg cells has been demonstrated in mouse models of inflammation, cancer, transplantation, and particularly in autoimmunity. In this review, we focus on the recent advances that lead to the understanding of the development and function of Breg cells and the implications of B cells in human autoimmune diseases. Cellular & Molecular Immunology (2013) 10, 122–132; doi:10.1038/cmi.2012.60; published online 7 January 2013 Keywords: autoimmune disease; interleukin-10; regulatory B cells INTRODUCTION we review the recent literature studying both the phenotypic and B-cell development in the bone marrow is a dynamic and com- functional characterization of Breg cells and the implications B plex process involving a delicate balance between cell proliferation cells have on the pathogenesis of autoimmune diseases. and apoptotic selection. This balance results in the generation of functional B cells that are responsible for eliciting humoral IDENTIFICATION OF BREG CELLS 1–3 immunity. The concept that suppressor B cells could regulate Despite the observations made in the 1970s that B cells with the immune response originated in 1974, when the ability of B suppressive functions possibly existed, the potential role of B cells to suppress delayed-type hypersensitivity responses in guinea cells with regulatory functions in inflammatory and auto- 4,5 pigs was described. However, the term ‘regulatory B cells’, immune diseases has only been recently appreciated. Janeway which defines B-cell subsets with regulatory properties, was first and colleagues first observed that B10.PL mice lacking B cells introduced by Mizoguchi and Bhan nearly 30 years later.6 Similar suffered an unusually severe and chronic form of experimental to regulatory T (Treg) cells, the regulatory function of B cells is autoimmune encephalomyelitis (EAE), indicating that B cells exerted via the production of regulatory cytokines, such as IL-10 have regulatory properties in a mouse model of EAE.12 and TGF-b, and the ability to express inhibitory molecules that Subsequently, it was found that B cells affected this auto- suppress pathogenic T cells and autoreactive B cells in a cell-to- immune disease by regulating IL-10.13 Mizoguchi and Bhan cell contact-dependent manner.7 Until recently, the exact origin were the first to introduce the term ‘regulatory B cells’ to and molecular identity of regulatory B (Breg) cells remained elu- describe these B-cell subsets with regulatory properties.6 sive. Accumulating evidence suggests that the Breg cell population While studying the putative pathogenic role of B cells in the is heterogeneous, meaning that this population can be derived development of colitis, the authors unexpectedly observed that from all B cells under the correct stimulatory context and time.8 It T cell receptor alpha (TCRa)2/2 mice that were crossed with B has been postulated that Breg cells can exert their suppressive cell-deficient mice spontaneously developed an earlier onset of functions with different mechanisms in various mouse models colitis that was more severe compared to TCRa2/2 mice.14 of disease, including inflammation, cancer and autoimmunity.9 Moreover, Mizoguchi et al. further demonstrated that a certain Moreover, dynamic changes in Breg cells have been associated B-cell subset from gut-associated lymphoid tissues in a chronic with the progression of human autoimmune diseases.10,11 Here, inflammatory environment secreted IL-10, upregulated 1Department of Pathology and Center for Infection and Immunology, The University of Hong Kong, Hong Kong, China and 2Department of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, China 3These authors contributed equally to this work. Correspondence: Dr LW Lu, Department of Pathology and Center for Infection and Immunology, The University of Hong Kong, Pokfulam Road, Hong Kong, China. Received: 14 October 2012; accepted: 6 November 2012 Regulatory B cells in autoimmune diseases M Yang et al 123 expression of CD1d and suppressed the progression of intest- characterized human Breg cells with the phenotype inal inflammation by downregulating inflammatory cascades CD24hiCD271, which is a phenotype related to memory B associated with IL-1 and signal transducer and activator of cells.11 transcription 3 (STAT3) activation.15 Although great progress has been made in the characteriza- Early studies have revealed that B-1 cells in the peritoneal tion of Breg cells, the cell surface markers and/or specific tran- cavity are a major source of B cell-derived IL-10.16 Upon IL- scription factor(s) that are unique to Breg cells have not been 12 stimulation, B1a cells, but not B-1b cells, have the ability defined in mice and humans. Most of the currently identified to produce IL-10.17 Recently, the production of Th2 cyto- Breg cells exert their suppressive function at least partially kines by conventional B2 cells has been extensively investi- through the production of regulatory cytokines, such as IL- gated. The marginal-zone (MZ) B cells have been shown to 10 and TGF-b. This production of regulatory cytokines has regulate immunity by producing IL-10 in response to CpG been demonstrated by both in vitro functional assays and in stimulation in a mouse model of lupus.18 Moreover, splenic vivo mouse studies. transitional 2-MZ precursor (T2-MZP) B cells that express high amounts of CD21, CD23, CD24, IgM and CD1d from BREG CELLS IN AUTOIMMUNE DISEASES both naive and arthritic mice are capable of producing IL- The regulatory functions of Breg cells have been extensively 10. Remarkably, the regulatory function of T2-MZP cells characterized in various animal models of inflammation, can- depends on IL-10 production because T2-MZP cells from cer and autoimmune diseases. B cells are generally considered IL-102/2 DBA mice show no protection against the develop- to play a pathogenic role in the development of autoimmune 19 diseases because B cells produce autoantibodies that cause tar- ment of arthritis. Tedder and colleagues have identified a 26 subset of IL-10-producing B10 cells that contain the unique get tissue damage. However, autoantibodies can also exert a hi 1 protective effect via the clearance of apoptotic cells and reduc- phenotype CD1d CD5 . These cells share certain pheno- 27 typic markers with B-1a, MZ B and T2-MZP cells.20 B10 tion of autoantigen load. Moreover, B cells also act as anti- gen-presenting cells, which are cells that contribute to the cells normally represent 1%–2% of splenocytes in wild-type activation and amplification of naive, activated and autoreac- mice and approximately 10% in hCD19 transgenic mice. tive T-cell responses.28–30 It has been reported that antigens Notably, IL-10 production has been found to be restricted presented by resting B cells can induce the differentiation of to this B10 cell subset. Interestingly, IL-10 production was tolerogenic CD41 T cells.31,32 Furthermore, B cells, similar to T decreased in CD192/2 mice but increased in hCD19 trans- cells, can be defined as B effector 1 and 2 cells. B effector 1 cells genic mice. Rafei et al. have reported a Breg cell subset produce Th1-associated pro-inflammatory cytokines, includ- induced by a granulocyte-macrophage colony-stimulating ing tumor-necrosis factor (TNF)-a, IFN-c and IL-12, whereas factor–IL-15 fusion protein known as GIFT15.21 These B effector 2 cells produce Th2-associated cytokines, including GIFT15-induced Breg cells possess a phenotype akin to IL-4 and IL-13.33 Notably, certain regulatory B cells that pro- B10 and T2-MZP Breg cells. A study by Ding et al.revealed duce IL-10 or TGF-b have recently been shown to possess that T-cell Ig domain and mucin domain protein 1 (TIM-1) 6 inhibitory functions in autoimmune diseases. Thus, current is expressed by a large majority of IL-10-producing Breg B studies on the functional implications of Breg cells in the cells, which consist of a heterogeneous population including hi 1 pathogenesis of autoimmune diseases can facilitate the transitional B, MZ B, FO B and CD1d CD5 B10 cells. development of combined therapies for autoimmune diseases. TIM-11 B cells express IL-4 and IL-10, promote Th2 res- 22 In the following sections, the role of Breg cells in mouse models ponse and directly transfer allograft tolerance. Recently, of various autoimmune diseases, including rheumatoid arth- Qian et al. have reported that regulatory dendritic cells can ritis, autoimmune diabetes, autoimmune encephalomyelitis program splenic T1, T2, MZ and B1 cells to differentiate into and lupus, will be discussed. a distinct regulatory B-cell subset with the phenotype hi hi CD19 FccIIb . This B-cell subset exerts potent regulatory Breg cells in experimental arthritis functions, such as the secretion of IL-10 both in vitro and in Rheumatoid arthritis (RA) is a chronic inflammatory disease 23 vivo. that is characterized by inflammation in the synovium. This Aside from mouse Breg cells, the existence of human Breg inflammation is associated with the infiltration of activated T cells has recently been revealed.
Load more

Recommended publications
  • Intrinsic and Extrinsic Mechanisms for B-Cell Lymphoma Development and Progression Studied by Global Gene Expression Profiling
    From the Department of Laboratory Medicine Karolinska Institutet, Stockholm, Sweden INTRINSIC AND EXTRINSIC MECHANISMS FOR B-CELL LYMPHOMA DEVELOPMENT AND PROGRESSION STUDIED BY GLOBAL GENE EXPRESSION PROFILING Gustav Arvidsson Stockholm 2019 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Universitetsservice US-AB © Gustav Arvidsson, 2019 ISBN 978-91-7831-518-5 Intrinsic and extrinsic mechanisms for B-cell lymphoma development and progression studied by global gene expression profiling THESIS FOR DOCTORAL DEGREE (Ph.D.) By Gustav Arvidsson Principal Supervisor: Opponent: Professor Anthony Wright Professor Mikael Sigvardsson Karolinska Institutet Lund University Department of Laboratory Medicine Department of Laboratory Medicine Clinical Research Center Division of Molecular Haematology Co-supervisor: Examination Board: Professor Birgitta Sander Professor Lars-Gunnar Larsson Karolinska Institutet Karolinska Institutet Department of Laboratory Medicine Department of Microbiology, Tumor and Cell Division of Pathology Biology Associate Professor Ingrid Glimelius Uppsala University Department of Immunology, Genetics and Pathology Associate Professor Fredrik Öberg Uppsala University Department of Immunology, Genetics and Pathology For E and E ABSTRACT Mantle cell lymphoma (MCL) is a rare hematopoietic malignancy characterized by frequent relapses and poor survival, partly due to minimal residual disease, whereby a subset of malignant cells, harbored in protective niches, survive treatment. In vitro and ex vivo experiments have shown that MCL cells can be rescued from apoptosis through interactions with non-malignant cells such as stromal cells. The present thesis investigates the effect that extrinsic microenvironmental interactions may exert on MCL cells and discuss the presumptive role of these as well as intrinsic mechanisms in the development and progression of lymphomas.
    [Show full text]
  • B Cell Subsets in Autoimmune Disease B Cell Subsetsb Cell in Autoimmune Disease
    Thesis for doctoral degree (Ph.D.) 2018 Thesis for doctoral degree (Ph.D.) 2018 (Ph.D.) degree doctoral Thesis for B cell subsets in autoimmune disease B cell subsets in autoimmune disease B cell in autoimmune subsets Katrin Habir Katrin Habir From DEPARTMENT OF MEDICINE Karolinska Institutet, Stockholm, Sweden B CELL SUBSETS IN AUTOIMMUNE DISEASE Katrin Habir Stockholm 2018 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Printed by Eprint AB 2018 © Katrin Habir, 2018 ISBN 978-91-7676-900-3 B CELL SUBSETS IN AUTOIMMUNE DISEASE THESIS FOR DOCTORAL DEGREE (Ph.D.) AKADEMISK AVHANDLING som för avläggande av medicine doktorsexamen vid Karolinska Institutet offentligen försvaras i CMM Lecture Hall, L8:00, Center for Molecular Medicine (CMM), Karolinska Universitetssjukhuset, Solna. Friday February 2nd 2018 at 09.00 by Katrin Habir Principal Supervisor: Opponent: Dr. Stephen Malin Associate Professor Bengt Johansson Lindbom Karolinska Institutet Lunds Universitet Department of Medicine Department of Experimental Medical Science Division of Cardiovascular Medicine Division of Adaptive Immunity Co-supervisors: Examination Board: Professor Gunilla Karlsson Hedestam Professor Birgitta Heyman Karolinska Institutet Uppsala Universitet Department of Microbiology, Tumor and Cell Department of Medical Biochemistry and Biology Microbiology Division of Microbiology-Immunology Professor Dan Grandér Karolinska Institutet Associate Professor Lisa Westerberg Department of Oncology-Pathology Karolinska Institutet Department of Microbiology, Tumor and Cell Biology Associate Professor Angela Silveira Karolinska Institutet Department of Medicine Division of Cardiovascular Medicine “We still do not know one thousandth of one percent of what nature has revealed to us.” Albert Einstein THIS THESIS IS DEDICATED TO MY BELOVED ONES ABSTRACT B lymphocytes are a type of white blood cells, belonging to the adaptive arm of the immune system and involved in creating immunological memory.
    [Show full text]
  • Regulatory Lymphocytes: the Dice That Resolve the Tumor Endgame Subhadip Pati, Anandi Chowdhury, Sumon Mukherjee, Aharna Guin, Shravanti Mukherjee and Gaurisankar Sa*
    Pati et al. Applied Cancer Research (2020) 40:7 Applied Cancer Research https://doi.org/10.1186/s41241-020-00091-0 REVIEW Open Access Regulatory lymphocytes: the dice that resolve the tumor endgame Subhadip Pati, Anandi Chowdhury, Sumon Mukherjee, Aharna Guin, Shravanti Mukherjee and Gaurisankar Sa* Abstract A large number of cancer patients relapse after chemotherapeutic treatment. The immune system is capable of identifying and destroying cancer cells, so recent studies have highlighted the growing importance of using combinatorial chemotherapy and immunotherapy. However, many patients have innate or acquired resistance to immunotherapies. Long-term follow-up in a pooled meta-analysis exhibited long-term survival in approximately 20% of patients treated with immune checkpoint inhibitors or the adoptive transfer of chimeric T cells. It has been reported that high levels of immunoregulatory cells in cancer patients contribute to immunotherapy resistance via immunosuppression. Among the most important regulatory cell subtypes are the CD4+ T-regulatory cells (Tregs), identified by their expression of the well-characterized, lineage-specific transcription factor FOXP3. In addition to CD4+ Tregs, other regulatory cells present in the tumor microenvironment, namely CD8+ Tregs and IL10-producing B-regulatory cells (Bregs) that also modulate the immune response in solid and lymphoid tumors. These cells together have detrimental effects on tumor immune surveillance and anti-tumor immunity. Therefore, targeting these regulatory lymphocytes will be crucial in improving treatment outcomes for immunotherapy. Keywords: Breg, CTLA4, FOXP3, Immunotherapy, IL10, PDL1, Treg Background neo-antigens, which are not present in non-cancerous The suppression of anti-tumor immune responses and cells [5]. These neo-antigens offer a clinical advantage augmentation of tumor-promoting immune responses since the tumor cells expressing neo-antigens are then both contribute to tumor progression [1].
    [Show full text]
  • An Overview of B Cells – from Discovery to Therapy Mini Review
    An Overview of B Cells – from Discovery to Therapy Mini Review Immunology In the past two decades, significant advances have been made in B cell biology. These critical immune cells remain an active area of research particularly because disruption of B cell development or function results in a number of autoimmune diseases and malignancies. In addition to producing antibodies, B cells are professional antigen presenting cells that can present antigens to T cells to generate effective immune responses. B cells are however, a heterogeneous population of cells at different stages of maturation along the lineage, each with unique functional properties. This mini-review provides a brief history of the discovery of B cells, as well as describes the characteristics of each B cell lineage and the processes of B cell development, maturation and activation. Finally, we highlight the application of B cell biology in the development of novel therapeutics for the treatment of B cell mediated diseases. Contents 1. A brief history of the discovery of B cells 2. B cell development and maturation 3. B cell activation and the humoral immune response 4. B cells as therapeutic targets 1. A brief history of the discovery of B cells B cells are an integral part of the adaptive immune response. They represent a distinct lineage, with separate and unique functions from T cells. In addition to producing antibodies, they perform critical immune functions such as generating immunological memory, antigen presentation and regulatory cytokine production. Our current understanding of B cell biology was initiated in 1965 with a landmark study by Max Cooper and Robert Good.
    [Show full text]
  • Regulatory B Cells Induce Formation of IL-10-Expressing T Cells in Mice with Autoimmune Neuroinflammation
    12598 • The Journal of Neuroscience, December 14, 2016 • 36(50):12598–12610 Neurobiology of Disease Regulatory B Cells Induce Formation of IL-10-Expressing T Cells in Mice with Autoimmune Neuroinflammation X Andrea Pennati,1* Spencer Ng,2* Yuanqiang Wu,3 Jordan R. Murphy,2 XJiusheng Deng,2 X Srikant Rangaraju,4 Seneshaw Asress,4 XJennifer L. Blanchfield,5 Brian Evavold,5 and XJacques Galipeau1 1Department of Medicine, University of Wisconsin School of Medicine and Public Health and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin 53706, Departments of 2Hematology and Medical Oncology, 3Neurology, and 4Microbiology and Immunology, Emory University, Atlanta, Georgia 30322, and 5Department of Oncology, Second Xiangya Hospital, Changsha 410011, Hunan, People’s Republic of China Although B cells are traditionally known for their role in propagating proinflammatory immune responses, their immunosuppressive effects have only recently begun to be appreciated. How these regulatory B cells (Bregs ) suppress the immune response remains to be ϩ worked out in detail. In this article, we show that Bregs can induce the formation of conventional FoxP3 regulatory T cells (Tregs ), as well ϩ ϩ as a more recently described CD49b CD223 regulatory T-cell subset, known as type 1 regulatory T cells (Tr1s). When Bregs are trans- ferred into mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, they home to the spleen and mesenteric lymph nodes, leading to an expansion of Tregs and Tr1 in vivo.Tregs and Tr1s are also found in greater proportions in the CNS of mice with EAE treated with Bregs and are correlated with the remission of symptoms.
    [Show full text]
  • Regulatory B Cells: Origin, Phenotype, and Function
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Immunity Perspective Regulatory B Cells: Origin, Phenotype, and Function Elizabeth C. Rosser1 and Claudia Mauri1,* 1Centre for Rheumatology Research, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK *Correspondence: [email protected] http://dx.doi.org/10.1016/j.immuni.2015.04.005 Regulatory B (Breg) cells are immunosuppressive cells that support immunological tolerance. Through the production of interleukin-10 (IL-10), IL-35, and transforming growth factor b (TGF-b), Breg cells suppress immunopathology by prohibiting the expansion of pathogenic T cells and other pro-inflammatory lympho- cytes. Recent work has shown that different inflammatory environments induce distinct Breg cell popula- tions. Although these findings highlight the relevance of inflammatory signals in the differentiation of Breg cells, they also raise other questions about Breg cell biology and phenotype. For example, what are the func- tional properties and phenotype of Breg cells? Can a Breg cell arise at every stage in B cell development? Is inflammation the primary requisite for Breg cell differentiation? Here, we use these questions to discuss the advances in understanding Breg cell biology, with a particular emphasis on their ontogeny; we propose that multiple Breg cell subsets can be induced in response to inflammation at different stages in development. Introduction 1974). However, the molecular or biochemical mechanism The hallmark of an effective immune response is inflammation. responsible for these initial observations was never character- After infection, the inflammatory response is critical for clearing ized, and the field of ‘‘suppressor’’ B cells was abandoned.
    [Show full text]
  • Molecular Regulation of Peripheral B Cells and Their Progeny in Immunity
    Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Molecular regulation of peripheral B cells and their progeny in immunity Mark R. Boothby,1,2 Emily Hodges,3 and James W. Thomas1,2 1Department of Pathology–Microbiology–Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA; 2Department of Medicine, Rheumatology Division, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA; 3Department of Biochemistry, Vanderbilt Genetics Institute, Nashville, Tennessee 37232, USA Mature B lymphocytes are crucial components of adap- potentials. A vast trove of findings illuminates the tran- tive immunity, a system essential for the evolutionary fit- scriptional regulation and chromatin modifications (for ness of mammals. Adaptive lymphocyte function requires convenience, referred to here as epigenetic) that program an initially naïve cell to proliferate extensively and its developmental progression from common lymphoid pro- progeny to have the capacity to assume a variety of fates. genitors (CLPs) to the establishment of the naïve popu- These include either terminal differentiation (the long- lations of mature T and B cells (e.g., for review, see lived plasma cell) or metastable transcriptional repro- Busslinger 2004; Champhekar et al. 2015). Similarly, the gramming (germinal center and memory B cells). In this process of diversifying subsets of T cells after their activa- review, we focus principally on the regulation of differen- tion has been studied and reviewed intensively (Glimcher tiation and functional diversification of the “B2” subset. and Murphy 2000; Fang and Zhu 2017; Henning et al. An overview is combined with an account of more recent 2018). Mature B lymphocytes also have the potential to advances, including initial work on mechanisms that distribute their progeny among several distinct fates or eliminate DNA methylation and potential links between intermediate states after they have encountered a ligand intracellular metabolites and chromatin editing.
    [Show full text]
  • Pathogen Manipulation of B Cells: the Best Defence Is a Good Offence
    REVIEWS Pathogen manipulation of B cells: the best defence is a good offence Katharina Nothelfer1–3, Philippe J. Sansonetti1,2,4 and Armelle Phalipon1,2 Abstract | B cells have long been regarded as simple antibody production units, but are now becoming known as key players in both adaptive and innate immune responses. However, several bacteria, viruses and parasites have evolved the ability to manipulate B cell functions to modulate immune responses. Pathogens can affect B cells indirectly, by attacking innate immune cells and altering the cytokine environment, and can also target B cells directly, impairing B cell-mediated immune responses. In this Review, we provide a summary of recent advances in elucidating direct B cell–pathogen interactions and highlight how targeting this specific cell population benefits different pathogens. pattern recognition receptors 4–6 (FIG. 1) Immunoglobulin B cells are essential components of the adaptive immune general (PRRs) . The A large, Y‑shaped protein that system, and they were first defined and distinguished activation of several B cell clones (termed polyclonal is produced by B cells. from T cells almost 50 years ago1. Both B cells and T cells B cell activation) and their subsequent differentiation Immunoglobulins exist in a recognize pathogens with antigen-specific receptors, into short-lived plasma cells results in the production membrane-bound form as B cell receptors or are secreted but they differ in their developmental pathways and of low-specificity antibodies, which are generally asso- as antibodies. functions during infections. T cells differentiate in the ciated with the beneficial effects of an early weakening thymus and orchestrate immune responses as CD4+ of infections7.
    [Show full text]
  • B Cells and the Th2-Type Immune Response to Helminths
    Review To B or not to B: B cells and the Th2-type immune response to helminths Nicola Harris1 and William C. Gause2 1 Swiss Vaccine Research Institute and Global Health Institute, Ecole Polytechnique Fe´de´ rale, Lausanne, Switzerland 2 Department of Medicine and Center for Immunity and Inflammation, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101, USA Similar T helper (Th)2-type immune responses are gen- specific host–parasite interactions that subsequently oc- erated against different helminth parasites, but the cur. Parasitic helminths are classified as cestodes (tape- mechanisms that initiate Th2 immunity, and the specific worms), nematodes (roundworms) or trematodes (flukes). immune components that mediate protection against Helminth parasites invade both mucosal and non-mucosal these parasites, can vary greatly. B cells are increasingly tissues, and comprise a broad spectrum of different patho- recognized as important during the Th2-type immune gens including: microfilaria, Strongyloides (threadworms), response to helminths, and B cell activation might be a Ancylostoma and Necator (hookworms), Trichuris (whip- target for effective vaccine development. Antibody pro- worms), Schistosoma, Taenia, Trichinella, Ascaris, and duction is a function of B cells during helminth infection Anasakis. The course of infection can vary greatly between and understanding how polyclonal and antigen-specific helminths. For example, certain filarial nematodes are antibodies contribute should provide important insights transmitted by mosquitoes and can occupy and obstruct into how protective immunity develops. In addition, B lymphatic vessels with chronic infection that causes ele- cells might also contribute to the host response against phantiasis, whereas other parasitic nematodes, such as helminths through antibody-independent functions in- whipworms, are strictly enteric and reside in the epithelial cluding, antigen presentation, as well as regulatory and layer of the large intestine.
    [Show full text]
  • Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions
    International Journal of Molecular Sciences Review Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions Francesca Arruga, Benjamin Baffour Gyau, Andrea Iannello , Nicoletta Vitale, Tiziana Vaisitti and Silvia Deaglio * Department of Medical Sciences, University of Turin, via Nizza, 52, 10126 Torino, Italy; [email protected] (F.A.); benjaminbaff[email protected] (B.B.G.); [email protected] (A.I.); [email protected] (N.V.); [email protected] (T.V.) * Correspondence: [email protected] Received: 1 January 2020; Accepted: 3 March 2020; Published: 6 March 2020 Abstract: Representing the major cause of morbidity and mortality for chronic lymphocytic leukemia (CLL) patients, immunosuppression is a common feature of the disease. Effectors of the innate and the adaptive immune response show marked dysfunction and skewing towards the generation of a tolerant environment that favors disease expansion. Major deregulations are found in the T lymphocyte compartment, with inhibition of CD8+ cytotoxic and CD4+ activated effector T cells, replaced by exhausted and more tolerogenic subsets. Likewise, differentiation of monocytes towards a suppressive M2-like phenotype is induced at the expense of pro-inflammatory sub-populations. Thanks to their B-regulatory phenotype, leukemic cells play a central role in driving immunosuppression, progressively inhibiting immune responses. A number of signaling cascades triggered by soluble mediators and cell–cell
    [Show full text]
  • A Novel IL-10-Producing Innate Lymphoid Cells (ILC10) in a Contact Hypersensitivity Mouse Model
    BMB Rep. 2016; 49(5): 293-296 BMB www.bmbreports.org Reports A novel IL-10-producing innate lymphoid cells (ILC10) in a contact hypersensitivity mouse model Hyuk Soon Kim1,#, Jong-Hwa Jang2,#, Min Bum Lee1, In Duk Jung1, Yeong-Min Park1,*, Young Mi Kim3,* & Wahn Soo Choi1,* 1Department of Immunology, School of medicine, Konkuk University, Chungju 27478, 2Department of Dental Hygiene, Hanseo University, Seosan 31962, 3College of Pharmacy, Duksung Women’s University, Seoul 01369, Korea The immunoregulatory cytokine Interleukin 10 (IL-10) protein cytokine profiles and transcription factors. The groups are is produced by various cells during the course of inflammatory typically named ILCs (ILC1s), ILC2s, and ILC3s on the basis of disorders. Mainly, it downregulates pro-inflammatory cytokines, their ability to produce T helper (Th) 1, Th2, and Th17 antigen presentation, and helper T cell activation. In this study, cell-linked cytokines, respectively (3, 4). Briefly, ILC1s express we show that the ratio of IL-10-producing cells was the transcription factor T-bet and produce interferon- (IFN-) significantly increased in lineage negative (i.e., not T, B, or (5). ILC2s critically depend on transcription factor GATA3 for leukocyte cell lineages) cells than in lineage positive cells in the development and production of Interleukin (IL)-5, IL-9, lymphoid and peripheral tissues. We further observed that IL-13 and Amphiregulin (6-8). ILC3s require the orphan IL-10-producing innate lymphoid cells (ILCs), here called firstly nuclear receptor RoRt and produce IL-22 and IL-17A (9). ILC10, were increased in number in oxazolone-induced The cytokine IL-10 is well known for regulating effector T contact hypersensitivity (CHS) mice.
    [Show full text]
  • B Cell Regulation in Cancer and Anti-Tumor Immunity
    OPEN Cellular & Molecular Immunology (2017) 14, 662–674 www.nature.com/cmi REVIEW B cell regulation in cancer and anti-tumor immunity Anushruti Sarvaria, J Alejandro Madrigal and Aurore Saudemont The balance between immune effector cells and immunosuppressive cells and how this regulates the tumor microenvironment has been well described. A significant contribution of immune regulatory cells, including regulatory T cells, to tumor progression has been widely reported. An emerging body of evidence has recently recognized a role for B cells in modulating the immune response to tumors and lymphoid malignancies. Regulatory B cells (Bregs) are a newly designated subset of B cells that have been shown to play a pivotal role in regulating immune responses involved in inflammation, autoimmunity and, more recently, cancer. Bregs can suppress diverse cell subtypes, including T cells, through the secretion of anti-inflammatory mediators, such as IL-10, and can facilitate the conversion of T cells to regulatory T cells, thus attenuating anti-tumor immune responses. Similar B-cell subpopulations have been reported to be recruited to the tumor but to acquire their immunosuppressive properties within the tumor bed and thereby attenuate anti-tumor immune responses. However, despite a pivotal role for Bregs in promoting inflammation and carcinogenesis, the phenotypic diversity of the cell surface markers that are unique to Bregs remains unclear in mice and humans. In this review, we summarize the characteristics of Bregs and review our current knowledge of
    [Show full text]