The origin and nature of age-associated B cells (ABCs) in mice is poorly understood. Here we show that their emergence requires MHC class II and CD40/CD40L interactions, and that they express a heterogeneous immunoglobulin repertoire comparable to nave follicular and marginal zone B cell subsets. In contrast to nave B cells, ABCs display significant somatic hypermutation in their VH and V genes, indicating prior antigen encounter. Gene expression analyses confirm that ABCs differ substantially from nave B cells, and instead share transcriptional characteristics with memory B cells. These observations suggest that ABCs are a distinct memory B cell subset that accumulates during T-cell dependent responses to diverse antigens during the life of an individual.
