Figure 1.

A putative model for the involvement of B cell helper T cells in T1D pathogenesis. 1) CXCR5⁺ islet antigen‐specific Tfh cells are induced in pancreatic lymph nodes and support islet AAb production by autoreactive B cells. 2) A subset of Tfh cells downregulates CXCR5 and upregulates chemokine receptors (CCR2, CCR5 and CX3CR1) to become Tph cells. 3) Following Tfh activation in GCs, cTfh and cTph become detectable in peripheral blood. 4) Tph cells home to inflamed pancreatic islets due to the presence of CCL2, CCL5 and CX3CL1. 5) In islets, Tph cells produce CXCL13, which attracts B cells, and IL‐21, which promotes B cell activation and local AAb production. 6) IL‐21 may also support the proliferation and survival of autoreactive cytotoxic CD8⁺ T cells which further drive beta‐cell destruction