Affinity maturation of antibody responses is mediated by differential plasma cell proliferation.

MacLean, Andrew J; Deimel, Lachlan P; Zhou, Pengcheng; ElTanbouly, Mohamed A; Merkenschlager, Julia; Ramos, Victor; Santos, Gabriela S; Hägglöf, Thomas et al. · Science · 2025

basic_science · Level V

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Abstract

Increased antibody affinity over time after vaccination, known as affinity maturation, is a prototypical feature of immune responses. Recent studies have shown that a diverse collection of B cells, producing antibodies with a wide spectrum of different affinities, is selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown. We found that PC precursors (prePCs) expressing high-affinity antibodies received higher levels of T follicular helper cell (T<sub>FH</sub> cell)-derived help and divided at higher rates compared with their lower-affinity counterparts once they left the germinal center. Our findings indicate that differential cell division by selected prePCs accounts for how diverse precursors develop into a PC compartment that mediates serological affinity maturation.

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