The zinc finger protein Gfi1 is implicated in the regulation of IgG2b production and the expression of Iγ2b germline transcripts

Gfi1 is a zinc finger transcription factor that is undetectable in B lymphocytes but its expression rises rapidly upon antigenic stimulation or treatment with lipopolysaccharide (LPS). Here we show that Gfi1(-/-) mice have higher serum levels of gamma isotype immunoglobulin than WT animals. When challenged with antigen, Gfi1(-/-) mice react with accelerated formation of PNA(+)/CD19(+) germinal center B cells and an increased production of antigen-specific IgG2a and IgG2b. Moreover, Gfi1(-/-) B cells secrete more IgG2a and IgG2b than WT cells and produce higher levels of I gamma 2b sterile germline transcripts when cultured with LPS. While the proliferative response to stimulation with anti-IgM antibodies and plasma cell differentiation was normal in Gfi1(-/-) B cells, we found that mRNA and protein levels of TGF beta 1 were significantly increased in the absence of Gfi1. TGF beta 1 has been shown to be essential for the regulation of IgG subclass production and was previously found to selectively stimulate IgG2b secretion. our findings reveal a new function of Gfi1 in the control of IgG isotype production.