Figure 2.

T cell-independent generation of IgA⁺ B cells in the GALT. In the isolated lymphoid follicles, dendritic cells (DCs) that sample luminal bacteria produce TGF-β. DCs also produce BAFF and APRIL to generate IgA⁺ B cells that home into the lamina propria (LP) and differentiate into IgA-producing plasma cells (PCs). In the LP, CD103⁺ cDC2 that sample luminal bacteria produce IL-6 and retinoic acid (RA). CX₃CR1⁺ cells produce BAFF and APRIL in response to nitric oxide (NO, produced by Tip-DCs and PCs) and TSLP [produced by intestinal epithelial cells (iECs)]. RORγt⁺ innate lymphoid cells (ILCs) induce Tip-DCs in an LTα1β2-dependent manner, which produce BAFF and APRIL by pDCs. In the presence of BAFF/APRIL, RA, and IL-6, IgM⁺ B cells generate IgA⁺ B cells, which differentiate into IgA-producing PCs.