Antigen-induced Fc receptor-dependent and -independent B cell desensitization. An elevation in [Ca2+]i is not sufficient and protein kinase C activation is not required for these pathways of surface IgM-mediated desensitization.
The interaction of an Ag ligand with its B cell surface Ig (sIg) receptor can occur via an FcR-dependent or -independent pathway. We previously found that transfected TNP-specific B cells undergo both Ca2+ signaling and desensitization upon interaction with the thymus-dependent Ag TNP-OVA. Similarly, we showed that these B cells can also be desensitized by cross-linking sIg to the Fc gamma R via the formation of an Ag-antibody bridge. Thus, Ag-specific B cells can be desensitized by two different Ag-dependent events, one mediated by Ag-sIg interaction and the other by sIg-Fc gamma R cross-linking. Inasmuch as Ag-sIg and sIg-Fc gamma R interactions lead to positive and negative signaling, it was of interest to determine whether B cell desensitization mediated by these interactions occurs by one of the well known signaling pathways in B cells. We found that Ag-induced changes in [Ca2+]i could be readily dissociated from Ag-induced desensitization, indicating that a Ca(2+)-independent pathway is likely responsible for this pathway of desensitization. To determine if PKC plays a role in B cell desensitization mediated by either Ag or sIg-Fc gamma R interaction, PKC was downregulated by long term exposure to 12-O-tetradecanoylphorbol 13-acetate or inhibited by exposure of cells to staurosporine. The PKC down-regulated and inhibited cells underwent similar Ag- and Fc gamma R-dependent desensitization compared to cells containing active PKC. Taken together, these data indicate that Ag-induced desensitization of B cell signaling likely involves an event(s) that occurs either upstream or independent of Ag-induced elevations in [Ca2+]i and PKC activation.
Lazarus
A H
AH
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
Mills
G B
GB
Crow
A R
AR
Delovitch
T L
TL
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000502:physiology; D015536:Down-Regulation; D004789:Enzyme Activation; D007075:Immunoglobulin M / Q000502:physiology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011961:Receptors, Fc / Q000502:physiology*; D015398:Signal Transduction; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D000941:Antigens; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D010047:Ovalbumin; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium