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Rapid, B Lymphoid-Restricted Engraftment Mediated by a Primitive Bone Marrow Subpopulation¹

A. Elena Searles^*, Suzanne J. Pohlmann, L. Jeanne Pierce^*, S. Scott Perry, William B. Slayton, Mariluz P. Mojica^§ and Gerald J. Spangrude^2,*,

Departments of ^* Oncological Sciences, Pathology, Pediatrics, and ^§ Human Genetics, University of Utah, Salt Lake City, UT 84132

Utilizing multiparameter flow cytometry, we have defined a subset of bone marrow cells containing lymphoid-restricted differentiation potential after i.v. transplantation. Bone marrow cells characterized by expression of the Sca-1 and c-kit Ags and lacking Ags of differentiating lineages were segregated into subsets based on allele-specific Thy-1.1 Ag expression. Although hematopoietic stem cells were recovered in the Thy-1.1^low subset as previously described, the Thy-1.1^neg subset consisted of progenitor cells that preferentially reconstituted the B lymphocyte lineage after i.v. transplantation. Recipients of Thy-1.1^neg cells did not survive beyond 30 days, presumably due to the failure of erythroid and platelet lineages to recover after transplants. Thy-1.1^neg cells predominantly reconstituted the bone marrow and peripheral blood of lethally irradiated recipients with B lineage cells within 2 weeks, although a low frequency of myeloid lineage cells was also detected. In contrast, myeloid progenitors outnumbered lymphoid progenitors when the Thy-1.1^neg population was assayed in culture. When Thy-1.1^low stem cells were rigorously excluded from the Thy-1.1^neg subset, reconstitution of T lymphocytes was rarely observed in peripheral blood after i.v. transplantation. Competitive repopulation studies showed that the B lymphoid reconstitution derived from Thy-1.1^neg cells was not sustained over a 20-wk period. Therefore, the Thy-1.1^neg population defined in these studies includes transplantable, non-self-renewing B lymphocyte progenitor cells.

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