Engagement of CD83 on B cells modulates B cell function in vivo.
The transmembrane glycoprotein CD83 is an important regulator of both thymic T cell maturation and peripheral T cell response. Recent studies suggested that CD83 is also involved in the regulation of B cell maturation, activation, and homeostasis. In this study, we show that in vivo overexpression of CD83 dose dependently interfered with the Ig response to thymus-dependent and thymus-independent model Ag immunization. CD83 deficiency, in contrast, which was restricted to B cells in mixed bone marrow chimeras, led to unchanged or even slightly increased Ig responses. Strikingly, the engagement of CD83 that is naturally up-regulated on wild-type B cells by injection of anti-CD83 mAb in vivo induced a 100-fold increase in the IgG1 response to immunization. Kinetic analysis revealed that CD83 had to be engaged simultaneously or shortly after the B cell activation through injection of Ag, to modulate the IgG1 secretion. Furthermore, using mixed bone marrow chimeras in which either selectively the B cells or the dendritic cells were CD83 deficient, we demonstrate that anti-CD83 mAb mediated its biologic effect by engaging CD83 on B cells and not on CD11c(+) dendritic cells. Taken together, we provide strong evidence that CD83 transduces regulatory signals into the very B cell on which it is expressed.
Kretschmer
Birte
B
Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
Lüthje
Katja
K
Schneider
Stefanie
S
Fleischer
Bernhard
B
Breloer
Minka
M
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D005362:Ficoll / Q000008:administration & dosage / Q000276:immunology; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D007136:Immunoglobulins / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D005362:Ficoll; D006241:Haptens; D006433:Hemocyanins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D009596:Nitrophenols; D000097802:CD83 Antigen; C042158:2,4-dinitrophenyl keyhole limpet hemocyanin