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.

doi:10.64898/2026.07.15.738751

bioRxiv · 10.64898/2026.07.15.738751

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.

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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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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. Germinal center-independent memory B cells provide rapid protection from lethal influenza challenges. https://doi.org/10.64898/2026.07.15.738751

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