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

Science. 2024 Dec 19:eadr6896. doi: 10.1126/science.adr6896. Online ahead of print.

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, are selected into the plasma cell (PC) pathway. How affinity-permissive selection enables PC affinity maturation remains unknown. We found that PC precursors (prePC) expressing high affinity antibodies received higher levels of T follicular helper (Tfh)-derived help and divided at higher rates than their lower affinity counterparts once they left the GC. Our findings indicated that differential cell division by selected prePCs accounts for how diverse precursors develop into a PC compartment that mediates serological affinity maturation.