Molecular basis for the inhibition of LPS induced differentiation by anti-immunoglobulin.

Abstract

The inhibition of mitogen induced differentiation by antibodies directed against cell surface immunoglobulins has been used as a polyclonal model system for the study of immune complex mediated down-regulation of the B cell response. The mechanism of this inhibition may also be similar to the ability of gamma globulins coupled to haptens to induce hapten specific B cell tolerance. By biosynthetic labeling of newly synthesized mRNA and of polypeptide chains, the molecular level of inhibition of lipopolysaccharide (LPS) induced B cell differentiation by whole anti-immunoglobulins (anti-Ig) has been examined. It was found that neither blast transformation nor initiation of DNA synthesis is prevented. However, the specific enhancement of transcription of the mu and kappa chain genes induced by LPS is inhibited resulting in the total abrogation of the increase in steady state level of mu s mRNA. In contrast, the basal level of transcription necessary for maintenance of the synthesis of mRNA for membrane IgM and IgD is not affected. Accordingly, it is the specific inhibition of enhanced initiation of RNA polymerases at the mu-delta gene complex which results in the previously documented decrease in IgM secretion. Moreover, since there is also no detectable C gamma transcription in cells stimulated with LPS in the presence of anti-Ig, the further differentiation of IgG secretion in LPS stimulated cells is also prevented.