Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection

• DOI: 10.1016/j.celrep.2025.115472
• Publication Date: 2025-04-04T21:16:33Z
• Authors: Cory A. Perugino; Hang Liu; Jared Feldman; Jess Marbourg; Thomas V. Guy; Anson Hui; Nicole Ingram; Julian Liebaert; Neha Chaudhary; Weiyang Tao; Catherine Jacob-D...; Blake M. Hauser; Zayd Mian; Anusha Nathan; Zezhou Zhao; Clarety Kaseke; Rhoda Tano-Menka; Matthew A. Getz; Fernando Senjobe; Cristhian Berrios; Onosereme Ofoman; Zachary Manickas-...; Duane R. Wesemann; Jacob E. Lemieux; Marcia B. Goldberg; Kerstin Nündel; Ann Moormann; Ann Marshak-Roths...; Regina C. Larocque; Edward T. Ryan; John A. Iafrate; Daniel Lingwood; Gaurav Gaiha; Richelle Charles; Alejandro B. Balazs; Aridaman Pandit; Vivek Naranbhai; Aaaron G. Schmidt; Shiv Pillai
• Keywords: Memory B cell; Naive B cell; Immunoglobulin D

Memory lymphocytes are durable cells that persist in the absence of antigen, but few human B cell subsets have been characterized terms durability. The relative durability eight non-overlapping sub-populations covering 100% all class-switched was interrogated. Only two long-lived populations persisted antigen. In addition to canonical germinal center-derived switched-memory with an IgD-CD27+CXCR5+ phenotype, a second, non-canonical, distinct memory population IgD-CD27-CXCR5+ DN1 also durable, exhibited unique TP63-linked transcriptional and anti-apoptotic signature, had low levels somatic hypermutation, more clonally expanded than cells. likely evolved preserve immunological breadth may represent counterparts rodent extrafollicular that, unlike cells, can enter centers facilitate antibody evolution.