Regulating Mechanism Of Transcription Factor Blimp-1 In Plasma Cell

B lymphocytes have several distinct development stages: pro-B cells, pre-B cells, immature B cells, mature B cells and plasma cells (memory B cells). Transcription factors play a key role in the course of pro-B cells to plasma cells. Commitment of hematopoietic stem cells into early B-cell lineage depends on several transcription factors, including E2A, EBA and Pax-5. In Bcl-6-/- mouse, germinal center formation was impared. Pax-5 transcription must be repressed to allow plasma-cell differentiation. XBP-1 and IRF4 transcription factors are required for plasmacytic differentiation.Plasma cells are terminally differentiated B cells and sole producer of antibodies, and they are crucial for effective humoral immune response. Although advances have been made in recent years, the understanding of regulating mechanism of plasma cell differentiation is still very limited. Transcription factors XBP-1 and IRF4 have been proved to be required for differentiation from mature B cells to plasma cells. Blimp-1(B-lymphocyte-induced maturation protein1), a 98-KDa transcriptional factor that contains five zinc finger motifs, is called"master regulator"of plasma cell differentiation. Expression of Blimp-1 in mature B cells is sufficient to trigger terminal differentiation, resulting in generation of Ab-secreting plasma cells. Blimp-1 represses the expression of both Pax-5 and Bcl-6, and transcription factor XBP-1 is repressed by Pax-5. Therefore, decreased expression of Pax-5 leads to increased expression of XBP-1. Repression of Bcl-6 and Pax-5 expression and expression of Blimp-1 and XBP-1 are important for the induction of differentiation from mature B cells to plasma cells. A recent microarray study showed that Blimp-1 down-regulates more than 220 genes and up-regulates more than 30 genes. Due to early embryonic lethality of Blimp-1 knock-out embryos, Shapiro-selef et al generated Blimp-1 conditional knock-out mice to study the function of Blimp-1. In Blimp-1 deficient mice, the numbers of IgM secreting cells and CD138+ cells were significantly...