INDUCTION OF STAT PROTEIN SIGNALING THROUGH THE CD40 RECEPTOR IN B-LYMPHOCYTES - DISTINCT STAT ACTIVATION FOLLOWING SURFACE IG AND CD40 RECEPTOR ENGAGEMENT

Cross-linking CD40 mediates B lymphocyte growth and differentiation an d regulates cell death pathways by an unknown mechanism. Previous repo rts have suggested that protein tyrosine kinase activity is critical f or CD40-mediated biologic responses. We show here that CD40 engagement on murine B cells results in the rapid tyrosine phosphorylation of th e STAT6 transcription factor and the trans-activation of a reporter ge ne containing and IFN-regulatory factor-1 STAT-binding site. In earlie r studies, surface Ig engagement was found to produce rapid activation of STAT6 accompanied by later induction of STAT1, which is not observ ed after CD40 ligation. Thus, these results define mitogenic receptor- specific induction of STAT proteins in B cells and identify a novel an d direct signal transduction pathway from the cell surface to the nucl eus activated in B cells stimulated through CD40 that regulates a gene previously shown to be involved in oncogenesis and programmed cell de ath.