BLIMP-1 OVERCOMES THE BLOCK IN IGM SECRETION IN LIPOPOLYSACCHARIDE ANTI-MU F(AB')(2)-CO-STIMULATED B-LYMPHOCYTES

A combination of signals transmitted through the antigen receptor, mem brane-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. (Cel l 1994. 77: 297) that the complex changes in gene activities accompany ing high levels of immunoglobulin secretion are under the common contr ol of a master regulator, Blimp-1 (B lymphocyte induced maturation pro tein). We show here that in naive mouse B cells stimulated with lipopo lysaccharide (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 g amma 1 sterile transcripts are, however, up-regulated after receptor c o-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 I gM secretion. Transfection of a Blimp-1 expression vector also induced IgM secretion. The data indicate that Blimp-1 is an important regulat or of immunoglobulin secretion by primary B cells, and suggest that it s level of expression may determine the differentiation to Ig-secretin g plasma cells or entrance and maintenance in the memory pool.