Signal transduction in human B cells initiated via Ig beta ligation.
Ig alpha and Ig beta heterodimers are non-covalently associated with Ig to compose the antigen receptor complexes on B cells. The demonstration that different sets of tyrosine kinases bind to the cytoplasmic tails of Ig alpha and Ig beta suggests that Ig alpha and Ig beta may activate distinct second messenger pathways. In this study, we examined the effects of mAbs against an exposed epitope of human Ig beta on pre-B and B cell triggering. Cross-linkage of Ig beta on B cells leads to activation of tyrosine kinases, hydrolysis of phosphatidylinositides, and elevation of intracellular Ca2+, effects qualitatively identical to those of anti-mu mAbs. Our observations thus indicate that cross-linking of Ig beta does not segregate signal transduction pathways connected with the cytoplasmic tails of Ig alpha and Ig beta. Ig alpha ligation has been reported to be more effective in triggering pre-B than B cells, whereas our results indicated that Ig beta ligation is more efficient in triggering B than pre-B cells. In addition to their activation properties, the anti-Ig beta mAbs effectively modulated B cell receptor complexes and blocked terminal differentiation of all plasma cell isotypes. The findings support the idea that anti-Ig beta could serve as a universal B cell immunosuppressant.
Nakamura
T
T
Department of Medicine, University of Alabama at Birmingham 35294.
Sekar
M C
MC
Kubagawa
H
H
Cooper
M D
MD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000378:metabolism*; D051925:CD79 Antigens; D002454:Cell Differentiation; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010750:Phosphoproteins / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell