BLIMP-I mediates extinction of major histocompatibility class II transactivator expression in plasma cells

Class II transactivator (CIITA), a coactivator required for class II major histocompatibility complex (MHC) transcription, is expressed in B cells but extinguished in plasma cells,This report identifies B lymphocyte-induced m aturation protein I (BLIMP-I), a transcriptional repressor that is capable of triggering plasma cell differentiation, as a developmentally regulated r epressor of CIITA transcription. BLIMP-I represses the B cell-specific prom oter of the human gene that encodes CI ITA (MHC2TA) in a binding site-depen dent manner. Decreased CIITA correlates with increased BLIMP-I during plasm a cell differentiation in cultured cells. Ectopic expression of BLIMP I rep resses endogenous mRNA for CIITA and the CIITA targets, class II MHC, invar iant chain and H2-DM (the murine equivalent of HLA-DM) in primary splenic B cells as well as 18-81 pre-B cells. Thus, the BLIMP-I program of B cell di fferentiation includes loss of antigen presentation via extinction of CIITA expression.