GC-Tfh cell induction by Langerhans cells in steady-state is antigen-dose dependent and IL-6 independent

Abstract We previously compared the contributions of different skin dendritic cell subsets in the induction of humoral immune responses. We found that antigen delivery without adjuvants to Langerhans cells (LCs) through the c-type lectin receptor Langerin, unlike cDC1, induces germinal center T follicular helper cells (GC-Tfhs), GC B cells, and high antibody titers. We also showed that targeting LCs with higher antigen dose induced significantly lower B cell responses and antibody titers. To better understand the role of antigen dose in this response, we assessed the T cell responses following targeting of LCs with different amounts of antigen. In accordance with the B cell responses, we found that GC-Tfh cell formation was also antigen dose-dependent. Using two-complementary approaches targeting IL-6-deficient LCs and targeting LCs in mice treated with neutralizing anti-IL-6 antibody, we showed that LCs induced GC-Tfh cells’ formation is an IL-6 independent fashion. In summary, this study shows that targeting LCs at steady-state induces the formation of GC-Tfh cells through an antigen-dose dependent and IL-6 independent mechanism.