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The Blood Contains Multiple Distinct Progenitor Populations with Clonogenic B and T Lineage Potential¹

The Scripps-Florida Research Institute, Jupiter, FL 33458

The thymus is seeded by bone marrow-derived progenitors that circulate in the blood. Multiple cell types can be found in the thymus early after i.v. administration or in steady state, but most fail to satisfy the known characteristics of true T progenitors. Cells that do conform to classical definitions retain multilineage potential, but surprisingly, cannot make B cells. Because acquisition of the T lineage fate among noncommitted progenitors is a lengthy process, the absence of B cell potential in early thymocytes suggests that B and T lineages diverge prethymically. To test this suggestion, we screened numerous presumptive progenitor populations for T cell growth and differentiation potential, as well as for clonogenic T or B cell development. We find that blood and marrow each contain multiple distinct subsets that display growth and differentiation potential consistent with being canonical T progenitors. Assessment of clonogenic potential further shows that although all blood and marrow populations have high T cell cloning potential, no T/non-B cells are apparent. These data suggest that either true thymic reconstitution potential derives from a small T/non-B cell subset of one of these populations, or that most of the cells defined as canonical progenitors within the thymus do not, in fact, reside in the mainstream of T progenitor differentiation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Public Health Service Grants AI33940 and AI64665.

² Address correspondence and reprint requests to Dr. Howard T. Petrie, Scripps-Florida, 5353 Parkside Drive, RF-1, Jupiter, FL 33458. E-mail address: hpetrie{at}scripps.edu

³ Abbreviations used in this paper: BM, bone marrow; DP, double positive; DN, double negative; CLP, common lymphoid progenitor; MPP, multipotent progenitor.