DIFFERENTIAL EFFECT OF B-LYMPHOCYTE-INDUCED MATURATION PROTEIN (BLIMP-1) EXPRESSION ON CELL FATE DURING B-CELL DEVELOPMENT

The B lymphocyte-induced maturation protein (Blimp-l) upregulates the expression of syndecan-1 and J chain and represses that of c-myc, We h ave transfected Blimp-1 into two sublines of the BCL1 B cell lymphoma that represent distinct stages of B cell development in secondary lymp hoid tissues. After interleukin (IL)-2 and IL-5 stimulation, the BCL1 3B3 cells differentiate into centrocyte-like cells, whereas the BCL1 5 B1b cells blast and appear to be blocked at the centroblast stage. Thi s blasting effect and the increase in IgM secretion that follows it ca n be blocked by a dominant negative form of Blimp-1. At the same time, the ectopic expression of Blimp-1 in these partially activated cells induces an apoptotic response that also can be suppressed by the same dominant negative protein. A similar effect was noticed when Blimp-1 w as expressed in the mature L10A and the immature WEHI-231 lines, indic ating this may be a general effect at earlier stages of the B cell dev elopment, and distinct from the ability of Blimp-1 to induce maturatio n in late stages of differentiation. Truncation mutants indicate that the induction of the apoytotic response relies mainly on 69 amino acid s within Blimp-1's proline-rich domain. We propose that Blimp-1 expres sion defines a checkpoint beyond which fully activated B cells proceed to the plasma cell stage, whereas immature and partially activated ce lls are eliminated at this point.