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Germinal center-independent memory B cells provide rapid protection from lethal influenza challenges

Cakan, E.; Nait Mohamed, F. A.; Hui, A.; Logan, E. C.; Ingram, N.; Alexander, C. A.; Smerczynski, J.; Gadiraju, C. V.; Barnes, E.; Mounier, D. A.; Walker, B. D.; Lingwood, D.; Pillai, S.

2026-07-21 immunology
10.64898/2026.07.15.738751 bioRxiv
Show abstract

Memory B cell recall responses are crucial for rapid protection from pathogens expressing previously encountered antigens. While germinal centers (GCs) contribute to durable B cell memory in many contexts, GC formation is attenuated or completely abrogated during some severe infections. Whether GC-independent responses generate functional memory B cells that may contribute to protective immunity remains unclear. Using mice lacking GCs, we identified a durable class-switched GC-independent memory B cell population that was generated dominantly through a T-cell-dependent response. Vaccine-induced non-GC memory B cells demonstrated greater diversity and provided humoral protection from matched and diverse vaccine-unmatched influenza viral challenges. These results identify a unique, durable, diverse, GC-independent memory B cell population that can mediate rapid protection from severe infections by mutable pathogens.

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