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 maturation protein 1 (BLIMP-1), a transcriptional repressor that is capable of triggering plasma cell differentiation, as a developmentally regulated repressor of CIITA transcription. BLIMP-1 represses the B cell–specific promoter of the human gene that encodes CIITA (MHC2TA) in a binding site–dependent manner. Decreased CIITA correlates with increased BLIMP-1 during plasma cell differentiation in cultured cells. Ectopic expression of BLIMP-1 represses endogenous mRNA for CIITA and the CIITA targets, class II MHC, invariant 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-1 program of B cell differentiation includes loss of antigen presentation via extinction of CIITA expression.