A Germinal Center-Independent Innate-Like Memory B Cell Compartment of B1 Origin
Villavicencio, P. M.; Bottermann, M.; Ortiz Isuiza, M.; Parikh, S. S.; Warner, J. E.; Alicea, A.; Zhou, E.; Prum, T.; Naili, H.; Liu, X.; Weldon, S. R.; Batista, F. D.
Show abstract
Memory B cells (MBCs) are a critical cellular reservoir for long-term humoral immunity. MBCs display heterogeneous isotypes and surface markers and can arise through both germinal center (GC)-dependent and GC-independent extrafollicular (EF) pathways. Both the mechanisms controlling EF MBC differentiation and the identities of the B cell populations from which EF MBCs derive remain poorly understood. To capture MBC diversity, we applied a broad selection strategy followed by transcriptional profiling, identifying a subset of MBCs characterized by minimal class switching, limited somatic hypermutation, and an innate-like gene signature. Using genetic models, we demonstrated that this subset arises independently of GC responses and derives from innate B1 cells. These innate-like MBCs differentiate into antigen-specific antibody-secreting cells and confer protection against lethal viral infection. Together, our findings define a previously unrecognized arm of MBC responses, demonstrating that innate B1 cells contribute a non-redundant antibody repertoire to protective immunological memory.
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