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-beta 1 and AID were required for IgA expression, and LPS contributed to TGF beta 1-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 TGF beta 1-induced IgA isotype expression in at least two ways: by stimulating AID transcription before CSR and by enhancing the IgA secretion rate after CSR.