Cell Rep. 2025 Apr 1;44(4):115472. doi: 10.1016/j.celrep.2025.115472. Online ahead of print.
ABSTRACT
Memory lymphocytes are durable cells that persist in the absence of antigen, but few human B cell subsets have been characterized in terms of durability. The relative durability of eight non-overlapping human B cell sub-populations covering 100% of all human class-switched B cells was interrogated. Only two long-lived B cell populations persisted in the relative absence of antigen. In addition to canonical germinal center-derived switched-memory B cells with an IgD–CD27+CXCR5+ phenotype, a second, non-canonical, but distinct memory population of IgD–CD27–CXCR5+ DN1 B cells was also durable, exhibited a unique TP63-linked transcriptional and anti-apoptotic signature, had low levels of somatic hypermutation, but was more clonally expanded than canonical switched-memory B cells. DN1 B cells likely evolved to preserve immunological breadth and may represent the human counterparts of rodent extrafollicular memory B cells that, unlike canonical memory B cells, can enter germinal centers and facilitate B cell and antibody evolution.
PMID:40173042 | DOI:10.1016/j.celrep.2025.115472
