Pivotal role for α _V integrins in sustained Tfh support of the germinal center response for long-lived plasma cell generation

Abstract

Significance The hallmark of protective immunity to infection and vaccination is the generation of long-lived plasma cells (LLPCs) secreting high-affinity antibodies. T follicular helper cells (Tfh) must be retained within specialized germinal center (GC) structures to provide essential help to B cells for LLPC generation. How such Tfh GC accumulation is sustained is unclear. We identify an ECM:α V integrin axis in the control of the GC reaction. In the absence of T cell α V integrins, Tfh are generated and can support early B cell responses but fail to accumulate within the GC, resulting in a striking absence of LLPCs. Targeting α V integrins may enable novel therapeutic control of Tfh GC numbers to boost immunity or mitigate Ab-mediated autoimmune pathology.