Figure 2.

Bacterial fragments or luminal antigens taken up by the gastrointestinal epithelium through TLR-mediated recognition, activate the epithelium to release factors like TSLP that are taken up by dendritic cells. These DC will secrete cytokines like APRIL, BAFF and TGF-β that will impact on mucosal B-cells. APRIL and BAFF will interact with B-cell receptors as explained in Figure 1 , while TGF-β interacts with receptors to activate Smads (small mothers against decapentaplegic) that are important regulators of B cell responses, including the formation of BLIMP1 that promotes B-cell terminal differentiation to IgA-secreting plasma cells. The TNFRSF13B on chromosome 17, encodes TACI receptor that signals through different transcription factors like NFAT, AP-1, and NF-kappa-B which then modulate B-cell activities, including (T-cell independent) class switch recombination ( Figure 3 ), and plasma cell differentiation. In the TNFRSF13B gene contains multiple mutations (indicated by lines) with C104R and A181E being the most frequently occurring ones and this results in altered level of TACI receptor expression and function of the B-cells.