MEMBRANE IMMUNOGLOBULIN RECEPTOR CROSS-LINKING INDUCES FOSB MESSENGER-RNA EXPRESSION IN MATURE B-LYMPHOCYTES - ASSEMBLY OF DISTINCT FOSB-CONTAINING NUCLEOPROTEIN COMPLEXES DURING B-CELL STIMULATION

We demonstrate herein that anti-Ig stimulation of Bal-17 B cells leads to a rapid and transient increase in fosB mRNA levels, with kinetics similar to those previously reported for members of the jun gene famil y. The coupling of fosB expression to known protein kinases that are a ctivated following membrane immunoglobulin receptor (mig) cross-linkin g was evaluated. Inhibition of src-protein tyrosine kinase activity by pretreatment of Bal-17 B cells with herbimycin A prevented subsequent anti-Ig-dependent increases in fosB mRNA levels. Moreover, inhibition of protein kinase C (PHC) by pretreatment of Bal-17 B cells with stau rosporine, H7, or by phorbol ester-induced down-regulation of PRC acti vity blocked anti-Ig-stimulated fosB gene expression. These findings s uggest that fosB expression is coupled to a mIg-mediated pathway that utilizes activated src-protein tyrosine kinases and PKC. Immunoblottin g of Bal-17 B cell extracts with anti-FosB antiserum revealed that mig cross-linking results in an increase in FosB protein levels. Moreover , immunoprecipitation of nondenatured Bal-17 B cell extracts indicated that FosB forms complexes in vivo with JunB and JunD and to a lesser extent with c-Jun. The anti-Ig-induced FosB/Jun complexes bind to seve ral distinct cis-acting DNA elements, including AP-1 and NF-AB, which have been implicated in regulating nuclear gene expression during B ce ll activation. Collectively, these results suggest that FosB plays a c entral role in regulating gene expression during anti-Ig-mediated B ce ll activation. (C) 1995 Academic Press, Inc.