Function in Support of Its B Cell Identity Pax5 Lymphoid-Specific
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PAX5 Expression in Acute Leukemias: Higher B-Lineage Specificity Than Cd79a and Selective Association with T(8;21)-Acute Myelogenous Leukemia
[CANCER RESEARCH 64, 7399–7404, October 15, 2004] PAX5 Expression in Acute Leukemias: Higher B-Lineage Specificity Than CD79a and Selective Association with t(8;21)-Acute Myelogenous Leukemia Enrico Tiacci,1 Stefano Pileri,2 Annette Orleth,1 Roberta Pacini,1 Alessia Tabarrini,1 Federica Frenguelli,1 Arcangelo Liso,3 Daniela Diverio,4 Francesco Lo-Coco,5 and Brunangelo Falini1 1Institutes of Hematology and Internal Medicine, University of Perugia, Perugia, Italy; 2Unit of Hematopathology, University of Bologne, Bologne, Italy; 3Section of Hematology, University of Foggia, Foggia, Italy; 4Department of Cellular Biotechnologies and Hematology, University La Sapienza of Rome, Rome, Italy; and 5Department of Biopathology, University Tor Vergata of Rome, Rome, Italy ABSTRACT (13, 16). PAX5 expression also occurs in the adult testis and in the mesencephalon and spinal cord during embryogenesis (17), suggesting an The transcription factor PAX5 plays a key role in the commitment of important role in the development of these tissues. hematopoietic precursors to the B-cell lineage, but its expression in acute Rearrangement of the PAX5 gene through reciprocal chromosomal leukemias has not been thoroughly investigated. Hereby, we analyzed routine biopsies from 360 acute leukemias of lymphoid (ALLs) and mye- translocations has been described in different types of B-cell malig- loid (AMLs) origin with a specific anti-PAX5 monoclonal antibody. Blasts nancies (18–23), and, more recently, PAX5 has also been shown to be from 150 B-cell ALLs showed strong PAX5 nuclear expression, paralleling targeted by aberrant hypermutation in Ͼ50% of diffuse large B-cell that of CD79a in the cytoplasm. Conversely, PAX5 was not detected in 50 lymphomas (24). -
Further Delineation of Chromosomal Consensus Regions in Primary
Leukemia (2007) 21, 2463–2469 & 2007 Nature Publishing Group All rights reserved 0887-6924/07 $30.00 www.nature.com/leu ORIGINAL ARTICLE Further delineation of chromosomal consensus regions in primary mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH) S Wessendorf1,6, TFE Barth2,6, A Viardot1, A Mueller3, HA Kestler3, H Kohlhammer1, P Lichter4, M Bentz5,HDo¨hner1,PMo¨ller2 and C Schwaenen1 1Klinik fu¨r Innere Medizin III, Zentrum fu¨r Innere Medizin der Universita¨t Ulm, Ulm, Germany; 2Institut fu¨r Pathologie, Universita¨t Ulm, Ulm, Germany; 3Forschungsdozentur Bioinformatik, Universita¨t Ulm, Ulm, Germany; 4Abt. Molekulare Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Germany and 5Sta¨dtisches Klinikum Karlsruhe, Karlsruhe, Germany Primary mediastinal B-cell lymphoma (PMBL) is an aggressive the expression of BSAP, BOB1, OCT2, PAX5 and PU1 was extranodal B-cell non-Hodgkin’s lymphoma with specific clin- added to the spectrum typical of PMBL features.9 ical, histopathological and genomic features. To characterize Genetically, a pattern of highly recurrent karyotype alterations further the genotype of PMBL, we analyzed 37 tumor samples and PMBL cell lines Med-B1 and Karpas1106P using array- with the hallmark of chromosomal gains of the subtelomeric based comparative genomic hybridization (matrix- or array- region of chromosome 9 supported the concept of a unique CGH) to a 2.8k genomic microarray. Due to a higher genomic disease entity that distinguishes PMBL from other B-cell non- resolution, we identified altered chromosomal regions in much Hodgkin’s lymphomas.10,11 Together with less specific gains on higher frequencies compared with standard CGH: for example, 2p15 and frequent mutations of the SOCS1 gene, a notable þ 9p24 (68%), þ 2p15 (51%), þ 7q22 (32%), þ 9q34 (32%), genomic similarity to classical Hodgkin’s lymphoma was þ 11q23 (18%), þ 12q (30%) and þ 18q21 (24%). -
Genomic Profiling of Adult Acute Lymphoblastic Leukemia by Single
SUPPLEMENTARY APPENDIX Genomic profiling of adult acute lymphoblastic leukemia by single nucleotide polymorphism oligonucleotide microarray and comparison to pediatric acute lymphoblastic leukemia Ryoko Okamoto,1 Seishi Ogawa,2 Daniel Nowak,1 Norihiko Kawamata,1 Tadayuki Akagi,1,3 Motohiro Kato,2 Masashi Sanada,2 Tamara Weiss,4 Claudia Haferlach,4 Martin Dugas,5 Christian Ruckert,5 Torsten Haferlach,4 and H. Phillip Koeffler1,6 1Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA; 2Cancer Genomics Project, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; 3Department of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University 4MLL Munich Leukemia Laboratory, Munich, Germany; 5Department of Medical Informatics and Biomathematics, University of Münster, Münster, Germany; 6Cancer Science Institute of Singapore, National University of Singapore, Singapore Citation: Okamoto R, Ogawa S, Nowak D, Kawamata N, Akagi T, Kato M, Sanada M, Weiss T, Haferlach C, Dugas M, Ruckert C, Haferlach T, and Koeffler HP. Genomic profiling of adult acute lymphoblastic leukemia by single nucleotide polymorphism oligonu- cleotide microarray and comparison to pediatric acute lymphoblastic leukemia. Haematologica 2010;95(9):1481-1488. doi:10.3324/haematol.2009.011114 Online Supplementary Data ed by PCR of genomic DNA and subsequent direct sequencing of SNP in a region of CNN-LOH in an ALL sample versus the corresponding Design and Methods matched normal sample (Online Supplementary -
Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade
Published OnlineFirst May 4, 2017; DOI: 10.1158/2159-8290.CD-17-0292 RESEARCH ARTICLE Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade Yi-Feng Gu1,2, Shannon Cohn1,2, Alana Christie2, Tiffani McKenzie2,3, Nicholas Wolff1,2, Quyen N. Do4, Ananth J. Madhuranthakam4, Ivan Pedrosa2,4, Tao Wang2,5, Anwesha Dey6, Meinrad Busslinger7, Xian-Jin Xie2,8, Robert E. Hammer9, Renée M. McKay1,2, Payal Kapur2,3, and James Brugarolas1,2 Downloaded from cancerdiscovery.aacrjournals.org on September 26, 2021. © 2017 American Association for Cancer Research. 17-CD-17-0292_p900-917.indd 900 7/20/17 10:05 AM Published OnlineFirst May 4, 2017; DOI: 10.1158/2159-8290.CD-17-0292 ABSTRACT Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 muta- tions, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl ) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with PAX8, a transcription factor frequently overexpressed in ccRCC, led to ccRCC of different grades. Bap1 -defi cient tumors were of high grade and showed greater mTORC1 activation than Pbrm1 -defi cient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1 , in Pbrm1 -defi cient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specifi c drivers of ccRCC and histologic grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCCs arise from Bowman capsule cells. -
A PAX5-OCT4-PRDM1 Developmental Switch Specifies Human Primordial Germ Cells
A PAX5-OCT4-PRDM1 Developmental Switch Specifies Human Primordial Germ Cells Fang Fang1,2, Benjamin Angulo1,2, Ninuo Xia1,2, Meena Sukhwani3, Zhengyuan Wang4, Charles C Carey5, Aurélien Mazurie5, Jun Cui1,2, Royce Wilkinson5, Blake Wiedenheft5, Naoko Irie6, M. Azim Surani6, Kyle E Orwig3, Renee A Reijo Pera1,2 1Department of Cell Biology and Neurosciences, Montana State University, Bozeman, MT 59717, USA 2Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA 3Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, School of Medicine; Magee Women’s Research Institute, Pittsburgh, PA, 15213, USA 4Genomic Medicine Division, Hematology Branch, NHLBI/NIH, MD 20850, USA 5Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA. 6Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, University of Cambridge, Cambridge CB2 1QN, UK. Correspondence should be addressed to F.F. (e-mail: [email protected]) 1 Abstract Dysregulation of genetic pathways during human germ cell development leads to infertility. Here, we analyzed bona fide human primordial germ cells (hPGCs) to probe the developmental genetics of human germ cell specification and differentiation. We examined distribution of OCT4 occupancy in hPGCs relative to human embryonic stem cells (hESCs). We demonstrate that development, from pluripotent stem cells to germ cells, is driven by switching partners with OCT4 from SOX2 to PAX5 and PRDM1. Gain- and loss-of-function studies revealed that PAX5 encodes a critical regulator of hPGC development. Moreover, analysis of epistasis indicates that PAX5 acts upstream of OCT4 and PRDM1. The PAX5-OCT4-PRDM1 proteins form a core transcriptional network that activates germline and represses somatic programs during human germ cell differentiation. -
Supplemental Materials ZNF281 Enhances Cardiac Reprogramming
Supplemental Materials ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression Huanyu Zhou, Maria Gabriela Morales, Hisayuki Hashimoto, Matthew E. Dickson, Kunhua Song, Wenduo Ye, Min S. Kim, Hanspeter Niederstrasser, Zhaoning Wang, Beibei Chen, Bruce A. Posner, Rhonda Bassel-Duby and Eric N. Olson Supplemental Table 1; related to Figure 1. Supplemental Table 2; related to Figure 1. Supplemental Table 3; related to the “quantitative mRNA measurement” in Materials and Methods section. Supplemental Table 4; related to the “ChIP-seq, gene ontology and pathway analysis” and “RNA-seq” and gene ontology analysis” in Materials and Methods section. Supplemental Figure S1; related to Figure 1. Supplemental Figure S2; related to Figure 2. Supplemental Figure S3; related to Figure 3. Supplemental Figure S4; related to Figure 4. Supplemental Figure S5; related to Figure 6. Supplemental Table S1. Genes included in human retroviral ORF cDNA library. Gene Gene Gene Gene Gene Gene Gene Gene Symbol Symbol Symbol Symbol Symbol Symbol Symbol Symbol AATF BMP8A CEBPE CTNNB1 ESR2 GDF3 HOXA5 IL17D ADIPOQ BRPF1 CEBPG CUX1 ESRRA GDF6 HOXA6 IL17F ADNP BRPF3 CERS1 CX3CL1 ETS1 GIN1 HOXA7 IL18 AEBP1 BUD31 CERS2 CXCL10 ETS2 GLIS3 HOXB1 IL19 AFF4 C17ORF77 CERS4 CXCL11 ETV3 GMEB1 HOXB13 IL1A AHR C1QTNF4 CFL2 CXCL12 ETV7 GPBP1 HOXB5 IL1B AIMP1 C21ORF66 CHIA CXCL13 FAM3B GPER HOXB6 IL1F3 ALS2CR8 CBFA2T2 CIR1 CXCL14 FAM3D GPI HOXB7 IL1F5 ALX1 CBFA2T3 CITED1 CXCL16 FASLG GREM1 HOXB9 IL1F6 ARGFX CBFB CITED2 CXCL3 FBLN1 GREM2 HOXC4 IL1F7 -
Kaderschmiede
2 |12 Kaderschmiede FWF START/Wittgenstein 2012: Exzellenz9 » TRP: Wider besseres Wissen » Frau in der Wissenschaft: Verena Jantsch- Plunger » Interview: Helmut Denk » Persönliche Paradigmen: Gerhard Herndl INHALT 20 TRP: WIDer BESSERES WISSEN 30 FraU IN Der WISSENSCHAFT: VERENA JANTSCH- PLUNGER KaDER- SCHMIEDE 6 FWF 12 STAWI 2012: EXZELLENZ9 KONTEXT EDITORIAL 27 ERC-Broschüre: Excellent Prospects 4 PROJEKTVORSTELLUNGEN 28–29 Statement of Principles for Scientific 5 BRIEF DES PRÄSIDENTEN Merit Review 35 THEMA INTERVIEW: 6–11 Kaderschmiede FWF PANOPTIKUM HELMUT DENK 30–34 Frau in der Wissenschaft FOKUS Verena Jantsch-Plunger 12–15 STAWI 2012: Exzellenz9 35–39 Interview 16–18 Kursbestätigung Helmut Denk 19 Das letzte NFN 40–41 International ausgezeichnet 20–21 Wider besseres Wissen Meinrad Busslinger 22–23 FWF-Infoveranstaltungen: 42–45 Persönliche Paradigmen Auf ein Neues! Friedrich Stadler im Gespräch 24 FWF-E-Book-Library mit Gerhard Herndl 25 Aufwertung der studentischen Mitarbeit 46–47 Unterwegs 26 The Journal of Universal Rejection Around the World EDITORIAL 42 PERSÖNLICHE PARADIGMEN: GERHARD HERNDL TRP: WIDer BESSERES WISSEN ms mas stb Der Forschungs-Kader » Bei der Verwendung des Wortes „Kader“ muss man als Autor vorsichtig sein. Zu ambivalent ist der Begriff besetzt, das Spek- trum reicht von negativ besetzten militärischen oder politischen Zusammenhängen bis hin zu positiv assoziierten Bereichen wie Sport sowie „positiv besetzten“ Eliten. Die Spitzenforschung mit ihren hoch qua- lifizierten Wissenschafterinnen und Wissenschaftern ist so eine Elite. Eine Kaderschmiede zu sein, ist also in ausgewählten Bereichen eine Auszeich- nung. So versteht es auch der FWF, wenn er im Zusammenhang mit seiner „Qualitätsselektion“ im Bereich wissenschaftlicher Projekte und ihrer da- hinter stehenden Personen als Kaderschmiede für Spitzenforschung be- 46 zeichnet wird. -
Repressing the Repressor: Fra1 Controls Plasma Cell Generation
www.impactjournals.com/oncotarget/ Oncotarget, Vol. 6, No. 20 Editorial Repressing the repressor: Fra1 controls plasma cell generation Dirk Mielenz , Bettina Grötsch and Jean-Pierre David B cell differentiation from the early commitment become quickly up-regulated upon B cell activation [5]. into the B lymphoid lineage in the bone marrow up In addition, c-Fos had been shown to promote Blimp1 to the differentiation into antibody secreting plasma expression [6]. However, the physiological relevance cells is tightly controlled by a transcriptional program of these observations was not demonstrated in vivo. We dominated by a cascade of repression. Indeed, each recently showed by gain and loss of function experiments step of B cell differentiation to mature B cells appears that Fra1 enhances activation induced cell death (AICD) to depend on transcription factors that, in addition to upon its induction in activated B cells, and as well limits promoting differentiation, repress key determinants of B cell proliferation [7]. Moreover, transgenic over- other hematopoietic lineages or even key regulators of expression of Fra1 blocks plasma cell differentiation the next or previous steps of B cell differentiation. For and immunoglobulin production in vitro and in vivo. instance, Pax5 that is required for early B cell commitment In accordance, mice with B cell-specific deletion of and maintenance of B cell identity acts by repressing the Fra1 show enhanced plasma cell differentiation in vitro differentiation of lymphoid precursor cells into the other and in vivo as well as exacerbated antibody responses. hematopoietic lineages [1]. Globally, key transcriptional Interestingly, transgenic Bcl2 overexpression alleviated regulators of B cell identity such as Pax5, Bcl6 or Bach2, Fra1 elicited AICD and corrected the B cell proliferation all inhibit the generation of antibody secreting plasma defect. -
PAX5-ELN Oncoprotein Promotes Multistep B-Cell Acute Lymphoblastic Leukemia in Mice
PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice Laura Jamroga,1, Guillaume Cheminb,1, Vincent Fregonaa, Lucie Costerc, Marlène Pasquetd, Chloé Oudinetb, Nelly Rouquiéa, Naïs Pradea,c, Stéphanie Lagardea,c, Charlotte Cressona, Sylvie Hébrarda, Ngoc Sa Nguyen Huub, Marina Bousquete, Cathy Quelene, Pierre Broussete, Stéphane J. C. Mancinif, Eric Delabessea,c, Ahmed Amine Khamlichib,2, Bastien Gerbya,2,3, and Cyril Broccardoa,2,3 aCentre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III Paul Sabatier (UPS), 31037 Toulouse, France; bInstitut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, Centre National de la Recherche Scientifique (CNRS), UPS, 31077 Toulouse, France; cLaboratoire d’Hématologie, Centre Hospitalier Universitaire (CHU) de Toulouse, 31000 Toulouse, France; dDepartment of Pediatric Hematology, CHU de Toulouse, 31000 Toulouse, France; eCRCT, INSERM, UPS, ERL5294 CNRS, Laboratoire d’Excellence Toulouse Cancer (TOUCAN), 31037 Toulouse, France; and fAix Marseille University, CNRS, INSERM, Institut Paoli-Calmettes (IPC), Centre de Recherche en Cancérologie de Marseille (CRCM), 13009 Marseille, France Edited by Brian J. Druker, Oregon Health & Science University, Portland, OR, and approved August 29, 2018 (received for review December 14, 2017) PAX5 is a well-known haploinsufficient tumor suppressor gene in found in more than one-third of human B-ALL (9–11). These al- human B-cell precursor acute lymphoblastic leukemia (B-ALL) and is terations result in loss of PAX5 expression and impairment of involved in various chromosomal translocations that fuse a part of DNA-binding activity and/or transcriptional activity of PAX5. -
Id3 Induces an Elk-1- and Caspase-8-Dependent Apoptotic Pathway In
ID3 INDUCES AN ELK-1- AND CASPASE-8-DEPENDENT APOPTOTIC PATHWAY IN SQUAMOUS CARCINOMA CELLS A Dissertation submitted to the Faculty of the Graduate School of Arts and Sciences of Georgetown University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biochemistry and Molecular & Cellular Biology By You-shin Chen, M.S. Washington, DC November 18, 2014 Copyright 2014 by You-shin Chen All Rights Reserved ii ID3 INDUCES AN ELK-1- AND CASPASE-8-DEPENDENT APOPTOTIC PATHWAY IN SQUAMOUS CARCINOMA CELLS You-shin Chen, M.S. Thesis Advisor: Dean S. Rosenthal, Ph.D. ABSTRACT Inhibitors of differentiation/DNA binding (Id) proteins are helix-loop-helix (HLH) transcription factors. The Id protein family (Id1-Id4) mediates tissue homeostasis by regulating cellular processes including differentiation, proliferation, and apoptosis. Previously, we found that Id3 induced apoptosis in immortalized human keratinocytes (Simbulan-Rosenthal et al., 2006), consistent with its role as a tumor suppressor (Richter et al., 2012; Schmitz et al., 2012). To investigate the role of Id3 in malignant SCC cells (A431), a tetracycline-regulated inducible system was used to induce Id3 in cell culture and mouse xenograft models. We found that upon Id3 induction, there was a decrease in cell number under low serum conditions, as well as in soft agar. Microarray, RT-PCR, immunoblot, siRNA, and inhibitor studies revealed that Id3 induced expression of Elk-1, an ETS-domain transcription factor, inducing procaspase-8 expression and activation. Id3 deletion mutants revealed that 80 C-terminal amino acids, including the HLH, are important for Id3-induced apoptosis. -
Ebf1-Mediated Down-Regulation of Id2 and Id3 Is Essential for Specification of the B Cell Lineage
Ebf1-mediated down-regulation of Id2 and Id3 is essential for specification of the B cell lineage Melissa A. Thala, Thiago L. Carvalhoa,TiHea, Hyung-Gyoon Kima, Hua Gaob, James Hagmanb, and Christopher A. Kluga,1 aDepartment of Microbiology, The University of Alabama-Birmingham, Birmingham, AL 35294; and bIntegrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206 Edited by Cornelis Murre, University of California, San Diego, La Jolla, CA, and accepted by the Editorial Board November 7, 2008 (received for review March 13, 2008) Gene knockout experiments in mice have suggested a hierarchical of E47 (13) or E12 (14) in non-B-lineage cell lines, suggest that model of early B cell commitment wherein E2A proteins (E47 and E2A activity is essential upstream of Ebf1. Similarly, the Pax5 E12) activate early B cell factor (Ebf1), which in turn activates promoter is bound by Ebf1 based on EMSA and Ebf1 can expression of the B cell commitment factor, Pax5. In IL-7 receptor transactivate the Pax5 promoter in transient co-transfection alpha (IL-7R␣) knockout mice, B cell development is blocked before assays (15, 16). Ebf1 is also present in Pax5-deficient pro-B cells B-lineage commitment at the prepro-B cell stage in adult animals. derived from Pax5Ϫ/Ϫ adult mice (17), suggesting that Ebf1 may In IL-7R␣؊/؊ prepro-B cells, E47 is expressed and yet is insufficient participate in the activation of Pax5 expression. Complicating the to transcriptionally activate the putative downstream target gene, simple hierarchical model where E2A induces expression of Ebf1. -
Coexpression and Relative Abundance Defined by B Cell
Stages of Germinal Center Transit Are Defined by B Cell Transcription Factor Coexpression and Relative Abundance This information is current as Giorgio Cattoretti, Rita Shaknovich, Paula M. Smith, of September 27, 2021. Hans-Martin Jäck, Vundavalli V. Murty and Bachir Alobeid J Immunol 2006; 177:6930-6939; ; doi: 10.4049/jimmunol.177.10.6930 http://www.jimmunol.org/content/177/10/6930 Downloaded from References This article cites 63 articles, 28 of which you can access for free at: http://www.jimmunol.org/content/177/10/6930.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 27, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Stages of Germinal Center Transit Are Defined by B Cell Transcription Factor Coexpression and Relative Abundance Giorgio Cattoretti,1*† Rita Shaknovich,‡ Paula M. Smith,† Hans-Martin Ja¨ck,§ Vundavalli V. Murty,*† and Bachir Alobeid* The transit of T cell-activated B cells through the germinal center (GC) is controlled by sequential activation and repression of key transcription factors, executing the pre- and post-GC B cell program.