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

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.