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230.Full.Pdf CD36 Is Differentially Expressed on B Cell Subsets during Development and in Responses to Antigen This information is current as Woong-Jai Won, Martin F. Bachmann and John F. Kearney of September 25, 2021. J Immunol 2008; 180:230-237; ; doi: 10.4049/jimmunol.180.1.230 http://www.jimmunol.org/content/180/1/230 Downloaded from References This article cites 45 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/180/1/230.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • 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 *average by guest on September 25, 2021 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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology CD36 Is Differentially Expressed on B Cell Subsets during Development and in Responses to Antigen1 Woong-Jai Won,*† Martin F. Bachmann,‡ and John F. Kearney2*† Of a number of mAbs made by immunization with sort-purified marginal zone (MZ) B cells, one was shown to recognize the mouse scavenger receptor CD36. Although CD36 is expressed by most resting MZ B cells and not by follicular and B1 B cells, it is rapidly induced on follicular B cells in vitro following TLR and CD40 stimulation. In response to T-independent and T-dependent Ag .challenge, we found that CD36 was expressed on IgM؉ plasma cells, but down-regulated on isotype-switched plasma cells in vivo Although development, localization, and phenotype of MZ B cells in CD36؊/؊ mice appeared normal, there was a minor block in the transitional stages of mature B cell development. In both primary and secondary Ab responses to heat-killed Streptococcus pneumoniae (R36A strain), both phosphoryl choline (PC)-specific IgM and IgG levels in CD36؊/؊ mice were slightly reduced compared with wild-type mice. In addition, mice deficient in both TLR2 and CD36 produced significantly reduced levels of anti-PC Downloaded from IgG titers than those of single gene-deficient mice, suggesting that they may cooperate in an anti-PC Ab response. Collectively, these results show that CD36 does not affect the development of B cells, but modulates both primary and secondary anti-PC Ab responses during S. pneumoniae infection similarly to TLR2. The Journal of Immunology, 2008, 180: 230–237. ature B cells in mammals are divided into three major loids (17, 21–27). A role for CD36 has also been suggested in the 3 B cell subsets, marginal zone (MZ), follicular (FO), pathogenesis of Alzheimer’s disease and atherosclerosis (18, 25, http://www.jimmunol.org/ M and B1 B cells, depending on surface phenotypes, lo- 28–30). Recent studies showed that CD36 enhances TLR2 signal- cation, and immunological functions (1–4). Although MZ and B1 ing to induce cytokine secretion by macrophages, although the B cells represent subpopulations of naive mature B cells, they play exact mechanism was not established (31, 32). an important role in early innate-like and primary Ab responses (1, Because CD36 is expressed uniquely on freshly isolated mature 2, 5). In particular, they respond quickly to T-independent (TI) MZ B cells and is induced to high levels on other mature B cell Ags, resulting in a rapid production of large numbers of short-lived subsets after stimulation in vitro, we investigated the role of CD36 plasma cells (6, 7). with respect to B cell development and function and examined a Previously, our laboratory identified two surface markers, CD9 possible cooperation between CD36 and TLR2 in Ab responses. and FCRL5 (Fc receptor-like 5), which help distinguish MZ B and by guest on September 25, 2021 B1 cells from FO B cells in mice (8, 9). Recently, we and others Materials and Methods showed by different approaches that CD36 is expressed on resting Mice MZ B cells, but not the majority of FO B cells (10, 11). CD36Ϫ/Ϫ mice were obtained from Dr. Maria Febbraio at the Lerner Re- CD36 is a Type BI scavenger receptor family member, which is search Institute (Cleveland, OH). T15 H chain knock-in and M167Id Ig expressed by a variety of cell types including endothelium, eryth- transgenic mice were obtained from Dr. Jim Kenny at National Institutes of Health (Bethesda, MD), and BALB/cJ, C57BL/6J, and TLR2Ϫ/Ϫ mice rocytes, platelets, adipocytes, dendritic cells, neutrophils, mono- Ϫ Ϫ were purchased from The Jackson Laboratories (33). CD36 / mice were cytes/macrophages, microglia, and muscle cells (12–20). CD36 backcrossed at least to the sixth generation to C57BL/6 mice. All mice binds multiple ligands including native and modified low density were bred, and maintained in our animal facilities at the University of lipoproteins, oxidized phosphoryl choline (PC) epitope, anionic Alabama at Birmingham (UAB). All studies and procedures were approved phospholipids, collagens, thrombospondin-1, and fibrillar ␤-amy- by the UAB Institutional Animal Care and Use Committee (IACUC). Flow cytometry All Abs were purchased from BD Biosciences unless specified. Spleen, *Division of Developmental and Clinical Immunology and †Department of Microbi- peritoneal cavity (PEC), peripheral blood, and bone marrow (BM) cells ology, University of Alabama at Birmingham, Bikminghan AL 35294; and ‡Cytos were prepared as single cell suspensions after RBC lysis, and stained with Biotechnology AG, Wagistr 25, Schlieren-Zurich, Switzerland FITC conjugated anti-mouse CD1d, CD19, CD23, B220, IgM (SBA), IgG1 Received for publication August 7, 2007. Accepted for publication October 3, 2007. (SBA), TLR2 (eBioscience), peanut agglutinin (Jackson Immunoresearch Laboratories); PE conjugated anti-mouse CD5, CD23, CD38, syndecan1, The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance IgD (SBA); biotin conjugated anti-mouse syndecan1; allophycocyanin- with 18 U.S.C. Section 1734 solely to indicate this fact. conjugated AA4.1 (eBioscience), Mac1. Alexa 647 and Alexa 488 conju- 1 gated CD9 and CD36, PE conjugated CD21, and biotinylated CD36 (MZ1) This work was supported in part by National Institutes of Health Grants CA13148 were made in our laboratory, according to the manufacturer’s instructions and AI14782. (Invitrogen Life Technologies and Pierce). FITC conjugated PC-Dextran 2 Address correspondence and reprint requests to Dr. John F. Kearney, Division of and PE conjugated M167 Id mAb were provided by Dr. Louis Rezanka at Developmental and Clinical Immunology, Department of Microbiology, SHEL 410, the National Institute on Aging (Baltimore, MD). Biotinylated mAbs were 1825 University Boulevard, University of Alabama, Birmingham, AL 35294-2182. incubated with streptavidin-allophycocyanin as a secondary reagent. Cells E-mail address: [email protected] were analyzed using FACSCalibur flow cytometer and plotted with Win- 3 Abbreviations used in this paper: MZ, marginal zone; FO, follicular; PEC, perito- MDI (Scripps Institute) software. neal cavity; BM, bone marrow; DC, dendritic cell; PLC, plasma cell; GC, germinal center; WT, wild type; KO, knock-out; TG, transgenic; PC, phosphoryl choline; PEC, Cell sorting and semi-quantitative RT-PCR peritoneal cavity. To examine mRNA transcripts by mouse B cell subsets, total spleen B cells Copyright © 2007 by The American Association of Immunologists, Inc. 0022-1767/07/$2.00 obtained after RBC lysis were stained with FITC-conjugated anti-CD23 www.jimmunol.org The Journal of Immunology 231 Downloaded from http://www.jimmunol.org/ FIGURE 2. Rapid induction of CD36 on B cells. A, Rapid induction of CD36 on both MZ and FO B cells. FACS-sorted MZ and FO B cells were incubated with B cell activating agents, LPS (10 ␮g/ml), or anti-CD40 (1 by guest on September 25, 2021 ␮g/ml), for 1–3 days, and CD36 was detected by flow cytometry. B, In- duction of CD36 on PEC B1 cells. FACS-sorted PEC B1a (CD5ϩB220lowMac1ϩ) or B1b (CD5ϪB220lowMac1ϩ) cells were incu- bated with LPS for 1–3 days. Gray-filled histogram indicates isotype-con- FIGURE 1. Unique expression of CD36 by MZ B cells. A, Surface trol staining. staining of mature B cells with anti-CD36 mAb (MZ1 clone). Spleen cells from BALB/cJ mice were stained with FITC ␣-CD23, PE ␣-CD21, bio- tinylated ␣-CD36. PEC-exudate cells were stained with FITC ␣-B220, PE ␣ ␣ -CD5, and biotinylated -CD36, then developed with SA-allophycocya- In vitro mitogenic stimulation nin. Gray filled histograms indicate isotype-control staining. B, Expression of CD36 mRNA transcripts by splenic mature B cells. mRNA levels of The sorted MZ and FO B cells were cultured for 1 to 3 days with LPS CD36 from MZ and FO B cells were detected by semi-quantitative RT- (Sigma-Aldrich), anti-CD40 (BD Biosciences), or synthetic TLR2 ligands PCR. As a positive control, ␤-actin PCR was amplified with the same such as FSL1 and Pam3Cys-SKKKK (EMC microcollections GmbH). CD36 expression was determined by flow cytometry using our Alexa 647- number of cycles in parallel. C, Immunohistological staining of CD36 in conjugated anti-mouse CD36 mAb (MZ1). mouse spleen section. Frozen spleen sections from BALB/cJ mouse were stained with MOMA1, then developed with 7-amino-4-methyl coumarin- Cytokine measurement 3-acetic acid goat-anti-rat IgG (Blue). Sections were blocked with normal rat serum, then stained with Alexa488 MZ1 (Green) or tetramethyl rhoda- Sorted cells were stimulated with various activation agents such as LPS, mine iso-thiocyanate IgM (Red).
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