Continually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers
Julia Merkenschlager, Riza-Maria Berz, Víctor Ramos, Maximilian Uhlig, Andrew J. MacLean, Carla R. Nowosad, Thiago Y. Oliveira, Michel C. Nussenzweig
Abstract
Abstract Follicular helper T cells (T FH ) mediate B cell selection and clonal expansion in germinal centers (GCs), and follicular regulatory T cells (T FR ) prevent the emergence of self-reactive B cells and help to extinguish the reaction. Here we show that GC reactions continually recruit T cells from both the naïve conventional and naive thymic regulatory T cell (Treg) repertoires. In the early GC, newly recruited T cells develop into T FH , whereas cells entering during the contraction phase develop into T FR cells that contribute to GC dissolution. The T FR fate decision is associated with decreased antigen availability and is modulated by slow antigen delivery or mRNA vaccination. Thus, invasion of ongoing GCs by newly developing T FH and T FR helps remodel the GC based on antigen availability.