Affinity maturation of antibody responses is mediated by differential plasma cell proliferation
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.
Authors
- Lachlan P. Deimel (ORCID: https://orcid.org/0000-0003-3803-871X)
- Michel C. Nussenzweig (ORCID: https://orcid.org/0000-0003-0592-8564)
- Christian T. Mayer (ORCID: https://orcid.org/0000-0002-0256-9650)
- Julia Merkenschlager (ORCID: https://orcid.org/0000-0001-6726-7939)
- Víctor Ramos (ORCID: https://orcid.org/0000-0001-7353-3420)
- Gabriela S. Silva Santos (ORCID: https://orcid.org/0000-0002-7482-7380)
- Pengcheng Zhou (ORCID: https://orcid.org/0000-0002-7736-2902)
- Thomas Hägglöf (ORCID: https://orcid.org/0000-0002-7751-0928)
- Mohamed ElTanbouly (ORCID: https://orcid.org/0000-0001-7985-3839)
- Anna Gazumyan (ORCID: https://orcid.org/0000-0002-5976-9717)
- Andrew J. MacLean (ORCID: https://orcid.org/0009-0008-8378-4141)
- B. Hernández (ORCID: https://orcid.org/0000-0003-1445-1729)
Institutions
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- National Cancer Institute (US)
- Center for Cancer Research (US)
- Rockefeller University (US)
Publication Details
- Journal
- Science
- Published
- 2024-12-19
- DOI
- https://doi.org/10.1126/science.adr6896
- Citations
- 28
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 6.49
Funders
- Howard Hughes Medical Institute
- Stavros Niarchos Foundation
- National Institutes of Health