Figure 3.

Hypothetical model of autoantibody production mediated by M cells. SFB is delivered to CD11b^hi and CD11b^hi CD11c^hi cell subsets in PP via M cell-mediated transcytosis. The M cells engulf SFB, which induces the differentiation of Tfh cells. Tfh cells egress from the PP and migrate to the systemic lymphoid tissues where autoimmune responses predominantly occur, leading to the production of autoantibodies to glucose-6-phosphate isomerase and thus, exacerbation of arthritis. It is unlikely that SFB induces Tfh differentiation by molecularly mimicking the glucose-6-phosphate isomerase antigen. C. jejuni also can be taken up by M cells. B cells directly recognize C. jejuni LOS, probably through Toll-like receptor 4 (TLR4) engagement, and produce LOS-specific antibodies. LOS is structurally homologous to GM1 ganglioside, which can lead to the production of anti-GM1 antibodies. Anti-GM1 antibodies are associated with some forms of GBS. Likely, C. jejuni-derived protein antigens are also involved in the pathogenesis of GBS through the activation of Tfh and B cells. Pancreatic acinar cells secrete GP2 to the lumen, where it binds FimH-positive bacteria. FimH-positive bacteria with GP2 are taken up by M cells via receptor GP2. Antigen-presenting cells (APCs) recognize GP2 on the surfaces of bacteria and start producing anti-GP2 autoantibodies. Anti-GP2 autoantibodies may target GP2-expressing pancreatic cells to cause pancreatitis.