IMMUNOBIOLOGY A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

We have discovered a distinct mature B-cell subset that accumulates with age, which we have termed age-associated B cells. These cells comprise up to 30% of mature B cells by 22 months. Despite sharing some features with other mature B-cell subsets, they are refractory to BCR and CD40 stimulation. Instead, they re-spond to TLR9 or TLR7 stimulation and divide maximally on combined BCR and TLR ligation, leading to Ig production and preferential secretion of IL-10 and IL-4. Although similar to follicular B cells in both B-lymphocyte stimulator (BLyS) re-ceptor expression and BLyS binding ca-pacity, these cells do not rely on BLyS for survival. They are neither cycling nor the result of intrinsically altered B lymphopoi-esis in aged BM, but instead appear to be generated from mature B cells that ex-haustively expand during the individual’s lifetime. Finally, they present Ag effec-tively and favor polarization to a TH17 profile. Together, these findings reveal that while the magnitude of the mature primary B-cell niche is maintained with age, it is increasingly occupied by cells refractory to BCR-driven activation yet responsive to innate receptor stimula-tion. (Blood. 2011;118(5):1294-1304