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

• 成果类型: Article
• 署名作者: MacLean, Andrew J.; Deimel, Lachlan P.; Zhou, Pengcheng; ElTanbouly, Mohamed A.; Merkenschlager, Julia; Ramos, Victor; Santos, Gabriela S.; Haeggloef, Thomas; Mayer, Christian T.; Hernandez, Brianna; Gazumyan, Anna; Nussenzweig, Michel C.
• 署名单位: Rockefeller University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Rockefeller University; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11160
• DOI: 10.1126/science.adr6896
• 发表日期: 2025-01-24
• 页码: 413-420
• 关键词: center b-cells; germinal-center; selection; antigen; DYNAMICS; generation; CHALLENGE; migration; myc

摘要

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.