Age-related alterations in the lymphohematopoietic and B-lineage precursor populations in NZB mice.

Abstract

Significant disturbances in B lineage populations of New Zealand Black (NZB) mice have been reported, both with respect to their phenotypes as well as to their function. Notably, there is a profound age-dependent decrease in B-cell precursors in this strain of lupus prone mice. In efforts to characterize the impact of this disturbance in disease, we performed an intensive phenotypic and B-cell population analysis in young and old NZB mice. Our results revealed that there was a significant age-dependent decrease in B cell precursors at all levels of the B-cell-lineage developmental pathway. Analysis of the proliferative capacity of these cell populations showed a comparative decrease in cycling activity in the B-cell-lineage populations of old NZB mice. Furthermore, these cell subsets were much more susceptible to spontaneous apoptosis when compared with similar populations from age-matched BALB/c or young NZB mice. Since the frequency of cells that express the interleukin-7 receptor (IL-7R) declines as NZB mice age, we hypothesize that impairment of IL-7R signal transduction pathways could contribute to severe perturbations of B-cell function in aged NZB mice.