Studies of Marrow Progenitor Abnormalities in Lupus-Prone Mice: II. Further Studies of NZB Thy 1 negLin neg Bone Marrow Cells

Abstract

Bone marrow cells from NZB mice were fractionated and enriched in cells lacking surface markers characteristic of mature lineages, termed Thy 1 neg 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 1 lo Lineage neg cells. The NZB Thy 1neg Lineageneg 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 1 neg Lineage neg cells, representing early B lineage cells, were less effective than Lip 6 neg Thy 1 neg Lineage neg cells in radioprotection. NZB marrow contains a great many more CFU-S than does marrow fram nonautoimmune strains. DBA/2 mice transplanted with Thy 1 neg 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 6 neg Thy 1 neg 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 1 neg 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 1 neg 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 1 neg Lineage neg marrow population which serve as progenitors of the cells which mediate NZB disease.