Studies of marrow progenitor abnormalities in lupus-prone mice. II. Further studies of NZB Thy 1(neg)Lin(neg) bone marrow cells.
Bone marrow cells from NZB mice were fractionated and enriched in cells lacking surface markers characteristic of mature lineages, termed Thy 1neg Lineage(neg) cells. These cells represent approximately 1% of all marrow cells and constitute a much greater fraction of the bone marrow than do Thy 1lo Lineage(neg) cells. The NZB Thy 1neg Lineage(neg) cells were able to protect nonautoimmune, histocompatible DBA/2 recipients from lethal doses of irradiation, suggesting that this subpopulation contained progenitor cells. Consistent with this observation, fractioned Lip 6+ Thy 1neg Lineage(neg) cells, representing early B lineage cells, were less effective than Lip 6neg Thy 1neg Lineage(neg) cells in radioprotection. NZB marrow contains a great many more CFU-S than does marrow from nonautoimmune strains. DBA/2 mice transplanted with Thy 1neg Lineage(neg) cells from NZB marrow had substantial numbers of CFU-S, much greater than controls. This CFU-S potential was found primarily in the Lip 6neg Thy 1neg Lineage(neg) fractionated marrow, suggesting that that population contained early progenitor cells that had not yet differentiated into B lineage cells. Both radioprotection and increased CFU-S were transmitted serially by bone marrow from DBA/2 recipients of Thy 1neg Lineage(neg) NZB marrow to secondary and tertiary (irradiated) DBA/2 recipients. Also serially transplanted were precursors of antibody forming cells. These findings suggest that NZB Thy 1neg Lineage(neg) marrow cells play a critical role in the development of the abnormal phenotype of NZB mice. However, because this probably is not a homogeneous population, additional work will be necessary to define the surface and molecular properties of the cell or cells within the NZB Thy 1neg Lineage(neg) marrow population which serve as progenitors of the cells which mediate NZB disease.
Schwieterman
W D
WD
Arthritis and Rheumatism Branch, National Institute of Arthritis, Metabolism and Digestive and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
Manoussakis
M
M
Klinman
D M
DM
Steinberg
A D
AD
D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D013154:Spleen / Q000166:cytology; D013234:Stem Cells; D014916:Whole-Body Irradiation