Studies of bone marrow progenitor cells in lupus-prone mice. I. NZB marrow cells demonstrate increased growth in Whitlock-Witte culture and increased splenic colony-forming unit activity in the Thy-1-, lineage- population.
Previous studies have demonstrated that NZB marrow can transfer features of autoimmunity. Therefore, we undertook a study of NZB marrow to determine whether it demonstrated any phenotypic abnormalities. In Whitlock-Witte cultures, NZB marrow cells generated nonadherent cells at low seeding densities, densities at which marrow from other strains did not generate nonadherent cells. In contrast, NZB marrow grew less well than controls in Dexter cultures. Inasmuch as the latter favor growth of granulocyte-macrophage precursors and the former B cells, these results suggest a possible skewing of NZB marrow cells toward lymphocyte production. Unfractionated marrow cells from NZB mice were found to produce 10-fold more splenic colonies in lethally irradiated recipients than marrow cells from control mice. This result was independent of the genotype of the recipient. When the progenitor Thy-1lo, Lin- marrow subpopulation was studied, NZB mice did not differ substantially from controls regarding splenic CFU. Therefore, Thy-1-, Lin- marrow cells were studied as a possible source of the excess splenic CFU in NZB mice. Indeed, the NZB Thy-1-, Lin- population contained 30-fold more splenic CFU than did the Thy-1-, Lin- population from control mice. These results suggest that NZB mice have unusual marrow progenitor cells; such cells may play a role in their autoimmune disease.
Cellular Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
W D
WD
Schwieterman
G M
GM
Wood
D E
DE
Scott
A D
AD
Steinberg
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis*; D002455:Cell Division; D002478:Cells, Cultured; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology*; D008177:Lupus Vulgaris / Q000209:etiology*; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D008814:Mice, Inbred NZB; D013154:Spleen / Q000276:immunology / Q000502:physiology*; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens