Rapid, B lymphoid-restricted engraftment mediated by a primitive bone marrow subpopulation

Utilizing multiparameter how cytometry, we have defined a subset of bone ma rrow cells containing lymphoid-restricted differentiation potential after i .v. transplantation. Bone marrow cells characterized by expression of the S ca-1 and c-kit Ags and lacking Ags of differentiating lineages were segrega ted into subsets based on allele-specific Thy-1.1 Ag expression. Although h ematopoietic stem cells were recovered in the Thy-1.1(low) subset as previo usly described, the Thy-1.1(neg) subset consisted of progenitor cells that preferentially reconstituted the B lymphocyte lineage after i.v. transplant ation. Recipients of Thy-1.1(neg) cells did not survive beyond 30 days, pre sumably due to the failure of erythroid and platelet lineages to recover af ter transplants. Thy-1.1(neg) cells predominantly reconstituted the bone ma rrow 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 proge nitors 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, re constitution of T lymphocytes was rarely observed in peripheral blood after i.v. transplantation. Competitive repopulation studies showed that the B l ymphoid reconstitution derived from Thy-1.1(neg) cells was not sustained ov er a 20-wk period. Therefore, the Thy-1.1(neg) population defined in these studies includes transplantable, non-self-renewing B lymphocyte progenitor cells.