Continually recruited naïve T cells contribute to the follicular helper and regulatory T cell pools in germinal centers.

Merkenschlager, Julia; Berz, Riza-Maria; Ramos, Victor; Uhlig, Maximilian; MacLean, Andrew J; Nowosad, Carla R; Oliveira, Thiago Y; Nussenzweig, Michel C · Nat Commun · 2023

basic_science · Level V

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Abstract

Follicular helper T cells (T<sub>FH</sub>) mediate B cell selection and clonal expansion in germinal centers (GCs), and follicular regulatory T cells (T<sub>FR</sub>) 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<sub>FH</sub>, whereas cells entering during the contraction phase develop into T<sub>FR</sub> cells that contribute to GC dissolution. The T<sub>FR</sub> 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<sub>FH</sub> and T<sub>FR</sub> helps remodel the GC based on antigen availability.

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