A B cell subset uniquely responsive to innate stimuli accumulates in aged mice (45.7)

Abstract

Abstract We have discovered a functionally distinct mature B cell subset that accumulates with age, comprising up to 30% of all mature B cells by 22 months. Despite sharing some features with other mature B cell subsets, these cells are refractory to BCR and CD40 stimulation. Instead, they respond to TLR-9 stimulation and divide maximally upon combined BCR and TLR ligation. Although similar to follicular B cells in both BLyS receptor expression and BLyS binding capacity, these cells do not rely upon BLyS for survival. Further, they are not the result of intrinsically altered B lymphopoiesis in aged bone marrow, but instead appear to be gradually generated from a small subset of mature B cells that exhaustively expand throughout the individual’s lifetime. Thus, while the magnitude of the mature primary B cell niche is maintained with age, it is increasingly populated by cells refractory to BCR-driven activation yet responsive to innate receptor stimulation. This shift may contribute to the diminished capacity for adaptive humoral responses and increased propensity for autoimmunity associated with aging.