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.