Brigham and Women's investigates "affinity birth" in B cells to expand antibody repertoire plasticity

[Brigham and Women's Hospital](https://app.allsci.com/organization/ASC-OH-0000000001183-1.0-1764853177) has received a [USD 3 million](https://reporter.nih.gov/project-details/11388452) NIH R01 grant from the National Institute of Allergy and Infectious Diseases to investigate whether B cells lacking initial antigen specificity can acquire new antibody recognition through somatic hypermutation — a process the investigators term "affinity birth". The four-year award, running through May 2030, funds work by principal investigator [Duane R. Wesemann](https://app.allsci.com/researcher/ASC-PR-0000073460396-1.0-1722657485) into a hypothesis that challenges a foundational assumption of adaptive immunity: that somatic hypermutation (SHM) refines pre-existing antigen recognition rather than generating it de novo. Germinal center B cells that lack measurable antigen binding are conventionally considered bystanders, unlikely to contribute meaningfully to affinity maturation. The funded research will examine whether these non-specific B cells can nonetheless undergo SHM-driven mutation and selection, acquiring new specificities through what the grant describes as a combinatorial expansion of accessible immunoglobulin variable gene segments. If supported, the concept would suggest the germinal center reaction is more permissive — and the antibody repertoire more plastic — than current models indicate. The translational implications are most direct for vaccine design: understanding whether and how new specificities can emerge from initially non-reactive B cell populations could inform immunogen strategies targeting pathogens where the pre-immune repertoire offers limited coverage, including HIV-1, which is referenced in the grant's scientific terms. The NIAID R01 reflects sustained institutional investment in germinal center biology at a time when rational vaccine design — particularly for highly mutable pathogens — remains a central challenge. Wesemann's laboratory at Brigham and Women's is positioned within a dense Boston-area immunology ecosystem that includes competing and complementary programs at Harvard Medical School, MIT, and the Ragon Institute. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/affinity-birth-brigham-and-womens-investigates)