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‐μ F(ab′)₂ show low levels of Blimp‐1 mRNA and no longer secrete Ig. Iγ1 sterile transcripts are, however, up‐regulated after receptor co‐ligation. Addition of interleukin (IL)‐2 and IL‐5 to LPS + anti‐μ 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.