Blimp‐1 overcomes the block in IgM secretion in lipopolysaccharide / anti‐μ F(ab′)₂‐co‐stimulated B lymphocytes

Abstract

A combination of signals transmitted through the antigen receptor, membrane-bound cell interaction molecules and cytokine receptors induces B cell proliferation and differentiation into immunoglobulin-secreting or memory cells. It has recently been suggested by Turner et al. (Cell 1994. 77: 297) that the complex changes in gene activities accompanying high levels of immunoglobulin secretion are under the common control of a master regulator, Blimp-1 (B lymphocyte-induced maturation protein). We show here that in naive mouse B cells stimulated with lipopolysaccharide (LPS) alone (which leads to high IgM production), Blimp-1 is highly expressed, while cells co-stimulated with LPS and anti-mu F(ab')2 show low levels of Blimp-1 mRNA and no longer secrete Ig. I gamma 1 sterile transcripts are, however, up-regulated after receptor co-ligation. Addition of interleukin (IL)-2 and IL-5 to LPS + anti-mu F(ab')2-treated primary B cells led to up-regulation of Blimp-1 and IgM secretion. Transfection of a Blimp-1 expression vector also induced IgM secretion. The data indicate that Blimp-1 is an important regulator of immunoglobulin secretion by primary B cells, and suggest that its level of expression may determine the differentiation to Ig-secreting plasma cells or entrance and maintenance in the memory pool.

Identification and expression profiles of prdm1 in medaka Oryzias latipes

“…Innate immune factors such as IL2 can induce the expression of Prdm1; Prdm1 represses IL2 expression in turn and initiates leukocyte development in mouse [60]. Perhaps Prdm1a play the same role in the immune system of fish as its homologues in mammal to induce development of B, T and NK cells [2,3,5,[8][9][10][11][12][13][14][15][16][17].…”

“…The repression activity of Prdm1 is needed for development and maturation of lymphoid cells in the mammal [2,3,5,[8][9][10][11][12][13][14][15][16][17]. Mammal Prdm1 inhibits the expression of genes such as IL-2, c-Fos, ifng, tbx21 and bcl6 [60,61].…”

“…Prdm1 or the betainterferon gene positive-regulatory domain I binding factor (PRDI-BF1) is also known as B lymphocyte-induced maturation protein (Blimp-1) [1,2]. Prdm1 was first described as a protein binding to the beta-interferon promoter and repressing beta-interferon expression [1], and later was identified as a protein which being expressed upon differentiation of B lymphocytes to plasma cells and importantly, playing major role in activation of mature B cells and differentiation of B cells into plasma cells [2][3][4][5][6][7]. Prdm1-induced maturation of lymphocytes is correlated with the ability of Prdm1 to repress numbers of genes critical for mature B cell identity and cellular proliferation [5,[8][9][10][11][12][13].…”

BLIMP1α, the master regulator of plasma cell differentiation is a tumor supressor gene in B cell lymphomas

“…The first indication of the importance of BLIMP1 in plasma cell differentiation was provided by the demonstration that ectopic expression of BLIMP1 in mouse B cell lines or in mouse primary splenocytes promoted a plasma cell-like phenotype 2,21 . Knockout mice with a conditional deletion in mature B cells of all five zinc finger domains of BLIMP1, showed normal B cell development and number 4 .…”

Plasmacytic Transcription Factor Blimp-1 Is Repressed by Bach2 in B Cells

“…An overexpression of Blimp-1 induces mature B cells to differentiate into plasma cells (7)(8)(9). On the other hand, Blimp-1-deficient B cells fail to become either plasma cells or memory B cells (10).…”