title: Reciprocal regulation of mucosal surface IgA+ B cells by Ig receptor cross-linking and CD40 ligand.
abstract: In the present study, we analyze the role of Ig receptor cross-linking in T cell-dependent stimulation of both preswitch (surface IgM+ (sIgM+/sIgD+) B cells and postswitch (sIgA+) B cells. We demonstrate that purified sIgA+ B cells pretreated with anti-IgA-dextran at low concentrations (10 and 100 ng/ml) exhibited an increased response to activated T cells, whereas pretreatment with higher doses (1 and 10 micrograms/ml) led to a profound suppression of IgA secretion (> or = 90%). The suppressive effect of anti-IgA-dextran was accentuated in the presence of IL-2 and attenuated in the presence of IL-4. Anti-IgA-dextran pretreatment had no effect on sIgA+ B cell survival. sIgM+/sIgD+ B cells pretreated with anti-IgD-dextran or anti-IgM-dextran did not show significant inhibition. The increased susceptibility of sIgA+ B cells, but not of sIgM+/sIgD+ B cells, to Ig cross-linking-mediated suppression was confirmed in cross-linking studies with the same Ab (anti-kappa-dextran). Importantly, anti-IgA-dextran-mediated suppression could be reversed by stimulation of sIgA+ B cells with fibroblasts expressing CD40L; such a reversal required persistent exposure to cells expressing high levels of CD40L. These studies imply that Ig receptor cross-linking renders postswitch sIgA+ B cells unresponsive to subsequent stimulation via activated T cells, but this unresponsiveness is overcome by a persistent high level CD40L signal.
authors: Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: R O
authors: RO
authors: Ehrhardt
authors: B
authors: B
authors: Gray
authors: R
authors: R
authors: Duchmann
authors: J K
authors: JK
authors: Inman
authors: W
authors: W
authors: Strober
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching; D007152:Immunologic Capping; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014162:Transfection
chemical_list: D000888:Antibodies, Anti-Idiotypic; D007070:Immunoglobulin A; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand; D015847:Interleukin-4