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

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.