Inhibitory coreceptors activated by antigens but not by anti-Ig heavy chain antibodies install requirement of costimulation through CD40 for survival and proliferation of B cells.
Ag-induced B cell proliferation in vivo requires a costimulatory signal through CD40, whereas B cell Ag receptor (BCR) ligation by anti-Ig H chain Abs, such as anti-Ig micro H chain Ab and anti-Ig delta H chain Ab, alone induces proliferation of B cells in vitro, even in the absence of CD40 ligation. In this study, we demonstrate that CD40 signaling is required for survival and proliferation of B cells stimulated by protein Ags in vitro as well as in vivo. This indicates that the in vitro system represents B cell activation in vivo, and that protein Ags generate BCR signaling distinct from that by anti-Ig H chain Abs. Indeed, BCR ligation by Ags, but not by anti-Ig H chain Abs, efficiently phosphorylates the inhibitory coreceptors CD22 and CD72. When these coreceptors are activated, anti-Ig H chain Ab-stimulated B cells can survive and proliferate only in the presence of CD40 signaling. Conversely, treatment of Ag-stimulated B cells with anti-CD72 mAb blocks CD72 phosphorylation and induces proliferation, even in the absence of CD40 signaling. These results strongly suggest that activation of B cells by anti-Ig H chain Abs involves their ability to silence the inhibitory coreceptors, and that the inhibitory coreceptors install requirement of CD40 signaling for survival and proliferation of Ag-stimulated B cells.
Hokazono
Yasuhisa
Y
Laboratory of Immunology, School of Biomedical Science, Department of Immunology, Medical Research Institute, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Adachi
Takahiro
T
Wabl
Matthias
M
Tada
Nobuhiko
N
Amagasa
Teruo
T
Tsubata
Takeshi
T
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000941:Antigens / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002453:Cell Cycle / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000276:immunology; D037102:Lectins / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009596:Nitrophenols / Q000494:pharmacology; D010648:Phenylacetates; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; C064228:CD72 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007143:Immunoglobulin Heavy Chains; D007146:Immunoglobulin lambda-Chains; D037102:Lectins; D009596:Nitrophenols; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; C026242:4-hydroxy-5-nitrophenyl acetic acid