Inhibition of B-cell receptor-antigen complex internalization by FcgammaRIIB1 signals.
Membrane-expressed immunoglobulins are B-cell receptors (BCR) for specific antigens (Ag). Upon Ag engagement of the BCR, B-cells are activated to internalize Ag-BCR complexes, process Ag and subsequently present Ag-peptides loaded in class II MHC. Due to the specific nature of the BCR, the cognate interaction between T-cells expressing Ag-specific T-cell receptor and these Ag-presenting B-cells occur in a highly regulated and precise manner. Accordingly, efficient control of T-cell activation may be achieved through regulation of Ag presenting B-cells. A potent form of regulation of lymphocyte responses is mediated by Ig end-product and anti-idiotypic antibodies via Fc-dependent mechanisms. In this communication, the authors present data that an anti-idiotype (anti-Id) Ab inhibits BCR-mediated internalization of specific Ag. Coupling of BCR to the cytoskeleton was also abortive in anti-Id Ab-treated B-cells. Inhibition by anti-Id Ab was dependent upon the presence of FcgammaRIIB1 on B-cells. As a result of anti-Id Ab suppression, B-cells were unable to initiate Ca2+ responses in Ag-specific T-cells. The results suggest that co-crosslinking of FcgammaRIIB1 and BCR inhibits cytoskeletal coupling and internalization of the Ag-BCR complex thereby preventing specific Ag presentation by B-cells. Anti-Id Ab may mediate a negative regulatory mechanism that suppresses B-cell-mediated Ag-specific T-cell activation.
Sato
K
K
The Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Ochi
A
A
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents; D003599:Cytoskeleton; D006241:Haptens / Q000276:immunology; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D003432:Cross-Linking Reagents; C080571:Fc gamma receptor IIB; D006241:Haptens; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D002118:Calcium