Stage-specific alterations in murine B lymphopoiesis with age

Abstract

Although it is reported that B lymphopoiesis declines with age, the precursor stage(s) affected and the age of onset are ambiguous. Each progressive phase of B cell differentiation has distinct requirements; therefore, precise identification of the stage(s) that decline would yield insight into the age-related mechanisms affecting humoral immunity. We analysed the composition of B lineage cells of mice 1, 4, 12 and 24 months of age using flow cytometry. Numbers of prepro-B and pro-B cells were unchanged, and a profound decrease occurred only in the numbers of pre-B cells. This decrease occurred in two distinct phases: between 1 and 4 months and between 12 and 24 months. Notably, the numbers of newly formed B cells did not decline in parallel, suggesting that mechanisms are established to overcome the deficiency of pre-B cells. Since the age-related changes are limited to the pre-B cell stage, we hypothesized that the impairment acts at the pro-B to pre-B transition. We therefore evaluated whether the pro-B cells or the supporting stromal cells, which are necessary for normal progression of this stage, changed with age. The ability of pro-B cells to proliferate in the presence of stromal cells was reduced by 24 months of age, as was the ability of the stromal cells to support pro-B cell proliferation. In contrast, the ability to mature into IgM+ cells was unchanged. Thus, strategies that supplement the stromal environment may enhance B lymphopoiesis in aged animals.