Journal
JOURNAL OF IMMUNOLOGY
Volume 198, Issue 5, Pages 1921-1927Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1601106
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Funding
- Intramural Research Program of the National Institutes of Health, National Institute on Aging
- National Institute of Allergy and Infectious Diseases [T32 AI055428]
- Department of the Army [PR130769]
- National Institute on Aging [R01 AG030227]
- CDMRP [PR130769, 672542] Funding Source: Federal RePORTER
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The origin and nature of age-associated B cells (ABCs) in mice are poorly understood. In this article, we show that their emergence required MHC class II and CD40/CD40L interactions. Young donor B cells were adoptively transferred into congenic recipients and allowed to remain for 1 mo in the absence of external Ag. B cells expressing the T-bet transcription factor, a marker for ABCs, were generated after multiple cell divisions from C57BL/6 donors but not from MHC class II- or CD40-deficient donors. Furthermore, old CD154 (CD40L)-deficient mice did not accrue ABCs, confirming that they arise primarily through T-dependent interactions. To determine what Igs ABCs express, we sequenced V-H and V kappa rearranged genes from unimmunized 22-mo-old C57BL/6 mice and showed that they had a heterogeneous repertoire, which was comparable to that seen in old follicular and marginal zone B cell subsets. However, in contrast to the follicular and marginal zone cells, ABCs displayed significant somatic hypermutation. The mutation frequency was lower than found in germinal center cells after deliberate immunization, suggesting that ABCs have undergone mild stimulation from endogenous Ags over time. These observations show that quiescent ABCs are Ag-experienced cells that accumulate during T cell-dependent responses to diverse Ags during the life of an individual.
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