AN INTERLEUKIN-2 SIGNAL RELIEVES BSAP (PAX5)-MEDIATED REPRESSION OF THE IMMUNOGLOBULIN-J CHAIN GENE

Cytokine regulation of B cell development was analyzed using interleuk in-2 (IL-2)-induced transcription of the J chain gene as a model syste m. A nuclear target of the IL-2 signal was identified as the Pax5 tran scription factor, BSAP, which recognizes a negative regulatory motif i n the J chain promoter. Functional assays showed that BSAP mediates th e silencing of the J chain gene during the early stages of B cell deve lopment, but repression is relieved during the antigen-driven stages i n a concentration-dependent manner by an IL-2-induced down-regulation of BSAP RNA expression. At the low levels present in J chain-expressin g plasma cells, BSAP repression could be overridden by positive-acting factors binding to downstream J chain promoter elements. Overexpressi on of BSAP in these cells reversed the positive regulation and inhibit ed J chain gene transcription. Thus, IL-2 regulation of BSAP concentra tion may provide a mechanism for controlling both repressor and activa tor functions of BSAP during a B cell immune response.