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-β1 and AID were required for IgA expression, and LPS contributed to TGFβ1-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 TGFβ1-induced IgA isotype expression in at least two ways: by stimulating AID transcription before CSR and by enhancing the IgA secretion rate after CSR.