Constitutive and regulated marrow adipocytes do not actively inhibit B lymphopoiesis

Adipocytes accumulate in the bone marrow with age. This has been proposed to trigger age-related changes in hematopoiesis that include a decline in B cell development. Bone marrow fat cells differ from adipocytes in other areas of the body and include 2 subsets termed constitutive and regulated adipocytes. These 2 types of marrow adipocytes have distinct properties and distribution across the skeleton. We assessed the contribution of each adipocyte subset to the loss of B cell progenitors and the age-related increase in hematopoietic stem cells (HSCs) and myeloid progenitors by quantifying their frequency and number in constitutive and regulated adipocyte containing bones from young and old animals. We also examined hematopoiesis in mice fed a high fat diet, which increases marrow adipose tissue, and quantified the expression of genes encoding inflammatory cytokines in constitutive and regulated adipocytes from young and old mice. The results indicated that marrow adipocytes do not actively drive the decline of B lymphopoiesis and other changes in hematopoiesis that occur with age. Instead, the findings support a model in which the age-related expansion of constitutive and regulated fat decreases marrow space available for blood cell production thereby reducing the number of cells from all lineages and stages of hematopoietic development.