A highly differentiated T follicular helper (Tfh) cell population in Peyer’s Patches promotes germinal center and IgG1 responses

T follicular helper cells (Tfh) are essential for the germinal center reaction and the production of high affinity antibodies. Tfh cells produce the cytokine IL-21, which is important for germinal center B cell proliferation and survival and the formation of plasma cells. To study IL-21 producing cells we developed an IL-21eGFP BAC transgenic mouse strain in which a gene encoding a diphteria toxin receptor (DTR)-eGFP fusion protein was placed under IL-21 transcriptional control. Using the new reporter strain we identified a GFP⁺ subpopulation of highly differentiated Tfh cells in Peyer’s Patches of the gut. Differentiation of GFP⁺ Tfh cells in Peyer’s Patches is highly dependent on the bacteria microbiota, especially on gram-positive bacteria. DT ablation of GFP⁺ T cells demonstrated that this Tfh subpopulation is necessary for optimal germinal center reaction and IgG1 responses in Peyer’s Patches.