We propose that Blimp-1 expression defines a checkpoint beyond which fully activated B cells proceed to the plasma cell stage, whereas immature and partially activated cells are eliminated at this point.ĭifferentiation of B lymphocytes into plasma cells depends on their continuous exposure to prodifferentiation and antiapoptosis signals. The majority of nonreactive and self-reactive clones are eliminated in the bone marrow at the pro– ( 1, 2) and pre–B stages ( 3). Once mature, the recruitment of new B cells to the long-lived recirculating B cell pool depends on a positive selection process that takes place in the splenic periarteriolar lymphoid sheath (PALS reference 4). Upon antigen encounter, these long-lived circulating cells are retained in secondary lymphoid organs. After being exposed to the appropriate T cell help, they proliferate and relocate to germinal centers ( 5), where they are subjected to negative selection before the onset of somatic mutation ( 6). The surviving cells interact with follicular dendritic cells that supply proliferative, antiapoptotic signals ( 7, 8) and upregulate the expression of multiple receptors required for T cell interaction ( 9, 10). The selected B cell clones then interact with T cells that provide them with additional survival signals, induce isotype switching ( 11, 12), and aid in their differentiation into plasma or memory cells.

Transcription factors that regulate the survival of developing B cells at different points along this pathway remain largely unknown. We have previously shown that IL-2 and IL-5 upregulate the expression of the B lymphocyte–induced maturation protein (Blimp-1) 1 in mature B cells ( 13). Blimp-1 and its human homologue PRDI-BF1 ( 14, 15) are zinc finger proteins that contain four Kruppel-like zinc fingers as well as a number of other domains that may mediate protein– protein interactions ( 13, 16).

Transfection of Blimp-1 into the BCL1 CW13.20-3B3 mature B cell line (hereafter referred to as 3B3) induces IgM secretion, J chain upregulation, and Syndecan-1 expression ( 13).

Blimp-1 has also been shown recently to regulate the expression of c-myc in mature B cells ( 17). During this transition phase, c-myc controls both proliferation and apoptosis ( 19), depending on signals provided by cytokines ( 20).Īs Blimp-1 is gradually upregulated from the mature B cell stage to the plasma cell ( 13), the expression of c-myc is progressively turned off ( 18).

Being quick on cw13