Anti-mu antibody blocks LPS driven B cell differentiation by suppressing specific mRNAs.

Abstract

High concentrations of anti-mu antibodies inhibit differentiation and increase proliferation of adult mouse splenic B cells stimulated by LPS. Cells from treated cultures express Ia antigens and on removal of anti-mu reexpress membrane IgM. They do not develop into plasmablasts secreting IgM. To investigate the mechanism of suppression we used Northern blots hybridized with cDNA probes to mu, kappa, J, and I-A beta chains to analyze RNAs in anti-mu suppressed and control cultures. Messenger RNAs for mu, kappa, and J chains but not I-A beta chain are diminished in anti-mu treated cells as compared to controls. Cells treated with anti-kappa antibodies have decreased mRNA levels for mu as well as kappa chains. Suppression mediated by modulation of the IgM receptor is not immunologically specific, but selectively inhibits expression of a cluster of unlinked genes which are coordinately activated during differentiation.