Figure 1.

T cell-dependent generation of IgA⁺ B cells in the GALT. In the PPs, dendritic cells (DCs) that engulf directly or indirectly (via antigen transfer by CX₃CR1⁺ cells) luminal bacteria produce IL-6 and move from the SED to the IFR, where they prime CD4⁺ T cells to generate follicular helper T (Tfh) cells, which are derived from Tregs and Th17 cells. Tfh cells move into the follicle, where they interact with IgM⁺ B cells in a cognate manner (MHC-TCR and CD40-CD40L). In addition, Tip-DCs induce the expression of TGF-β receptor (TGFβR) through their production of nitric oxide (NO). Subsequently, B cells differentiate into IgA⁺ B cells through AID expression in response to TGF-β, IL-21 (produced by Tfh cells), and RA (produced by DCs). IgA⁺ B cells migrate into the intestinal lamina propria (LP), where they differentiate into IgA-producing plasma cells.