The B-cell biology of aging.

Although both the number and responsiveness of peripheral B cells in aged mice remain relatively intact, there are dramatic changes in B-cell generation. Alterations in B-cell development include both a skewing of V-gene utilization, especially in cells responsive to phosphorylcholine, and a decrease in the generation of various developmental B-cell subsets. The altered representation of these subsets appears to be the consequence of two developmental blocks. The first developmental block occurs during the maturation of pro-B cells and is evidenced by a decrease in the number of pre-B cells. The second developmental block occurs at the earliest stage of sIg(+)-cell maturation (sIgMvery lo). Because of this block in B-cell maturation, in spite of a decrease in incoming pre-B cells, the number of sIgMvery lo cells appears to increase in aged mice. Additionally, the time of residence of cells within this maturational stage increases dramatically, while the proportion of cells in more mature (sIgMhi) stages of bone marrow development are decreased. In addition to the decreased number of maturing bone marrow B cells, the population of splenic B cells that represent recent bone marrow émigrés (HSAvery hi) is markedly decreased. In the face of this decrease in newly emerging cells from the bone marrow, the population of mature splenic B cells is maintained by their increased longevity.