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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-03-0733.
Submitted March 7, 2002
Accepted June 25, 2002
B cell development in the thymus is limited by inhibitory signals from the thymic microenvironment
Yoshiko Hashimoto, Encarnacion Montecino-Rodriguez, Hyosuk Leathers, Robert P Stephan, and Kenneth Dorshkind*
Department of Pathology and Laboratory Medicine and the Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA, USA
Department of Developmental and Clinical Immunology, University of Alabama, Birmingham, AL, USA
* Corresponding author; email: kdorshki{at}mednet.ucla.edu.
B cell precursors are present in the thymus, and the thymic microenvironment is the source of lymphopoietic factors that include IL-7. Despite the fact that they are bone marrow derived cells, the data in this report demonstrate that intrathymic B cell 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 interleukin 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.
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