Mechanisms underlying the effects of LPS and activation-induced cytidine deaminase on IgA isotype expression.
Activation-induced cytidine deaminase (AID) is needed for Ig class switch recombination (CSR). We explored the effect of LPS on the expression of AID during B cell differentiation, and the role of AID in IgA isotype expression. In normal spleen B cells, LPS increased AID transcription up to 48 h post-stimulation, i.e. around the time of Ig CSR. TGF-b1 and AID were required for IgA expression, and LPS contributed to TGFb1-induced IgA production largely by inducing AID. Interestingly, LPS repressed AID transcription in sIgA+ B cells but still stimulated IgA production mainly by increasing the rate of IgA secretion. Our data indicate that LPS contributes to TGFb1-induced IgA isotype expression in at least two ways: by stimulating AID transcription before CSR and by enhancing the IgA secretion rate after CSR.
Department of Microbiology, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
Seok-Rae
SR
Park
Hyun-A
HA
Kim
Sung-Ki
SK
Chun
Jae-Bong
JB
Park
Pyeung-Hyeun
PH
Kim
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000378:metabolism*; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007134:Immunoglobulin Switch Region; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007071:Immunoglobulin A, Secretory; D007132:Immunoglobulin Isotypes; D008070:Lipopolysaccharides; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase