Impaired Ability of Bone Marrow Stromal Cells to Support B-Lymphopoiesis With Age

Abstract

B-lymphopoiesis decreases with age. We studied how aging affects bone marrow stromal cells, because they provide the growth factors and cell contacts required for B-lymphopoiesis. No differences were noted in the cell-surface phenotype of young and old primary-cultured stromal cells. Fluorescence-activated cell sorter-purified stromal cells from old mice were deficient in the ability to support the proliferation of interleukin-7 (IL-7)–specific B-lymphoid cell lines. The kinetics of this response indicated that IL-7 was not immediately available from stromal cells of either age and was further delayed on aged stromal cells. The levels of IL-7 protein within stromal cells were equivalent between young and old animals, suggesting that the production of IL-7 was not altered by aging. Negligible amounts of IL-7 were found either freely secreted or in the extracellular matrix of cultures of young and old marrow. Contact between the lymphoid cells and the primary stromal cells was required for detectable proliferation, suggesting that cell contact was required for the release of IL-7. We propose that stromal cells regulate B-lymphopoiesis by limiting the amount of IL-7 available to the developing precursors. Therefore, we conclude that the age-related decrease in the function of bone marrow stromal cells is related to the impaired release of IL-7.

Early B-lymphocyte precursors and their regulation by sex steroids

“…Two previous studies concluded that B lymphocytes are made continuously throughout life in human bone marrow (55,57). This contrasts to the situation in mice where some investigators concluded that lymphopoietic activity is greatly reduced in old animals (66)(67)(68). While numbers of B-cell precursors within a given bone can be easily assessed in the mouse, absolute values are difficult to obtain for human bone marrow.…”

Immunosenescence: emerging challenges for an ageing population

“…123 Additionally, IL-7 receptor components seem to be expressed in Pro-and B cells derived from old mice at comparable levels to young mice. 124 Thus, IL-7 therapy alone might not work because of the inability to maintain this cytokine in the particular niche and/or signalling defects in the aged mice. In fact phosphorylated P-STAT5, a signal transducer from IL-7 and IL-2 receptor JAK activation, is likely to be crucial in anti-immunosenescence therapies because its presence is much reduced in both aged B-cell precursors 40 and ageing T cells.…”

Immunosenescence and macrophage functional plasticity: dysregulation of macrophage function by age‐associated microenvironmental changes

“…This finding suggests that part of the deficiency observed in macrophages from aged animals and humans might be caused by changes in the tissue environment. It is known that the stromal environments of the bone marrow, the spleen, the lymph nodes and the thymus change with age, resulting in reduced hematopoiesis, thymopoiesis, and peripheral homeostasis (1)(2)(3)(4)(5)(169)(170)(171)(172)(173)(174)(175)(176). Although myeloid dendritic cells in aged rodents and humans appear to be poorly immunogenic (8,10,141,142), fully functional myeloid dendritic cells can be generated in vitro from blood monocytes from aged donors (177).…”