Rapid, B lymphoid-restricted engraftment mediated by a primitive bone marrow subpopulation.
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-1.1low subset as previously described, the Thy-1.1neg subset consisted of progenitor cells that preferentially reconstituted the B lymphocyte lineage after i.v. transplantation. Recipients of Thy-1.1neg cells did not survive beyond 30 days, presumably due to the failure of erythroid and platelet lineages to recover after transplants. Thy-1.1neg 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-1.1neg population was assayed in culture. When Thy-1. 1low stem cells were rigorously excluded from the Thy-1.1neg 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-1.1neg cells was not sustained over a 20-wk period. Therefore, the Thy-1. 1neg population defined in these studies includes transplantable, non-self-renewing B lymphocyte progenitor cells.
Searles
A E
AE
Department of Oncological Sciences, University of Utah, Salt Lake City 84132, USA.
Pohlmann
S J
SJ
Pierce
L J
LJ
Perry
S S
SS
Slayton
W B
WB
Mojica
M P
MP
Spangrude
G J
GJ
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D002469:Cell Separation; D003114:Colony-Forming Units Assay; D006082:Graft Enhancement, Immunologic / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017710:Lymphocyte Transfusion; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D011828:Radiation Chimera / Q000276:immunology; D018800:Thy-1 Antigens / Q000096:biosynthesis
D018800:Thy-1 Antigens; D019009:Proto-Oncogene Proteins c-kit