The zinc finger protein Gfi1 is implicated in the regulation of IgG2b production and the expression of Igamma2b 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 Igamma2b 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 TGFbeta1 were significantly increased in the absence of Gfi1. TGFbeta1 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.
Igwe
Emeka
E
Institut für Zellbiologie Tumorforschung, IFZ, Universitätsklinikum Essen, Essen, Germany. emekaigwe@zbc.kgu.de
Kosan
Christian
C
Khandanpour
Cyrus
C
Sharif-Askari
Ehssan
E
Brüne
Bernhard
B
Möröy
Tarik
T
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology*; D018858:Germinal Center / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis*; D013601:T-Lymphocytes / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics; D016335:Zinc Fingers / Q000502:physiology*
D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D007074:Immunoglobulin G; D012333:RNA, Messenger; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1