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

Brigham and Women's Hospital has received a USD 3 million 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 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.

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