Affinity maturation of antibody responses is mediated by differential plasma cell proliferation
Andrew J. MacLean, Lachlan P. Deimel, Pengcheng Zhou, Mohamed ElTanbouly, Julia Merkenschlager, Víctor Ramos, Gabriela S. Silva Santos, Thomas Hägglöf, Christian T. Mayer, Brianna Hernandez, Anna Gazumyan, Michel C. Nussenzweig
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 FH 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.