title: Anti-CD83 promotes IgG1 isotype switch in marginal zone B cells in response to TI-2 antigen.
abstract: CD83 is a transmembrane glycoprotein that is rapidly up-regulated on activated B cells. Although CD83 itself is incapable to transduce intracellular signaling, it acts as a negative regulator of B cell function. We have recently described that a single application of anti-CD83 antibody results in dramatically enhanced production of antigen-specific IgG1 but not other isotypes upon immunization of mice with the TI-2 model antigen (Ag) NIP-Ficoll. This effect was mediated by the binding of anti-CD83 to CD83 on the surface of B cells themselves. In the current study we show that administration of anti-CD83 enhances IgG1-production independent of IL-4. Application of anti-CD83 does not alter the proliferation and general expansion of NIP-specific B cells. In the presence of anti-CD83, immunized mice develop normal frequencies of plasmablasts in response to NIP-Ficoll of which an increased number produces IgG1. These cells localize in extrafollicular foci in the spleen of immunized mice and originate from the marginal zone B cell pool. Taken together, our results indicate that CD83 engagement in vivo does not generally enhance B cell activation but selectively promotes IgG1 class switch in marginal zone B cells in response to TI-2 Ag.
authors.affiliation: Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Kretschmer
authors.affiliation: Chronic Immune Reactions, German Rheumatism Research Centre (DRFZ), 10117 Berlin, Germany; Molecular Immunology, Robert Koch Institute, 13353 Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Weber
authors.affiliation: Chronic Immune Reactions, German Rheumatism Research Centre (DRFZ), 10117 Berlin, Germany; Molecular Immunology, Robert Koch Institute, 13353 Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
authors.affiliation: Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; Institute for Immunology, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fleischer
authors.affiliation: Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
authors.forename: Minka
authors.initials: M
authors.lastname: Breloer
authors.affiliation: Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany. Electronic address: osterloh@bni-hamburg.de.
authors.forename: Anke
authors.initials: A
authors.lastname: Osterloh
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism; D007136:Immunoglobulins / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics; D013154:Spleen / Q000276:immunology; D015854:Up-Regulation; D000097802:CD83 Antigen; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D015703:Antigens, CD; D000955:Antigens, T-Independent; D007074:Immunoglobulin G; D007136:Immunoglobulins; D015847:Interleukin-4; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000097802:CD83 Antigen; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit
keywords: B lymphocytes; CD83; Class switch; TI