Growth inhibition of a B cell clone mediated by ligation of IL-4 receptors or membrane IgM.
The development of B cell tolerance is believed to involve negative signaling to the B cell derived from the binding of Ag to the B cell surface Ig (sIg). B cell clones that receive negative signals via sIg may provide useful models for studying the mechanisms of negative signaling. We have recently identified a previously undescribed mouse B cell clone, CHB3, which receives growth-inhibitory signals through the binding of IL-4 to its IL-4R or through ligation of its sIgM, but not its sIgD, molecules. Data presented here demonstrate that the negative signal delivered by sIgM, but not that delivered by IL-4R, requires protein kinase C activation and elevated intracellular Ca2+, and is associated with the tyrosine phosphorylation of a number of proteins. Thus, the IL-4R signaling pathway appears to be divergent from the sIgM-mediated pathway. However, growth inhibition mediated via both sIgM and IL-4R can be partially counteracted by a signal delivered through the MHC class II molecule.
Bishop
G A
GA
Department of Microbiology, University of Iowa, Iowa City 52242.
Ramirez
L M
LM
Koretzky
G A
GA
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells / Q000473:pathology; D006131:Growth Inhibitors / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007075:Immunoglobulin M / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000473:pathology; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000502:physiology*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D006131:Growth Inhibitors; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D014443:Tyrosine; D011493:Protein Kinase C; D002118:Calcium