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

Science. 2025 Jan 24;387(6732):413-420. doi: 10.1126/science.adr6896. Epub 2024 Dec 19.

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 (TFH 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.

MeSH terms

  • Animals
  • Antibody Affinity*
  • Antibody Formation*
  • B-Lymphocytes / immunology
  • Cell Proliferation*
  • Germinal Center* / cytology
  • Germinal Center* / immunology
  • Mice
  • Mice, Inbred C57BL
  • Plasma Cells* / cytology
  • Plasma Cells* / immunology
  • T Follicular Helper Cells* / immunology
  • T-Lymphocytes, Helper-Inducer / immunology