B-cell development in the thymus is limited by inhibitory signals from the thymic microenvironment

Abstract

B-cell precursors are present in the thymus, and the thymic microenvironment is the source of lymphopoietic factors that include interleukin-7 (IL-7). Despite the fact that intrathymic B-cell progenitors are bone marrow–derived cells, the data in this report demonstrate that these progenitors accumulate at an early pro–B-cell stage of development, cycle less than their bone marrow counterparts, and fail to differentiate efficiently. Additional studies presented herein indicate that these effects are mediated, at least in part, by soluble factors produced by the thymic microenvironment and suggest that they affect the ability of pro–B cells to respond optimally to IL-7. Taken together, these observations demonstrate a specific inhibition of intrathymic B lymphopoiesis, which in turn may explain why lymphoid cell production in the thymus is largely restricted to production of T-lineage cells despite the fact that B-cell precursors and B-lymphopoietic stimuli are present in that organ.