STUDIES OF MARROW PROGENITOR ABNORMALITIES IN LUPUS-PRONE MICE .2. FURTHER-STUDIES OF NZB THY 1(NEG)LIN(NEG) BONE-MARROW CELLS

Bone marrow cells from NZB mice were fractionated and enriched in cell s lacking surface markers characteristic of mature lineages, termed Th y 1(neg) Lineage(neg) cells. These cells represent approximately 1% of all marrow cells and constitute a much greater fraction of the bone m arrow than do Thy 1(lo) Lineage(neg) cells. The NZB Thy 1(neg) Lineage (neg) cells were able to protect nonautoimmune, histocompatible DBA/2 recipients from lethal doses of irradiation, suggesting that this subp opulation contained progenitor cells. Consistent with this observation , fractioned Lip 6(+) Thy 1(neg) Lineage(neg) cells, representing earl y B lineage cells, were less effective than Lip 6(neg) Thy 1(neg) Line age(neg) cells in radioprotection. NZB marrow contains a great many mo re CFU-S than does marrow from nonautoimmune strains. DBA/2 mice trans planted with Thy 1(neg) Lineage(neg) cells from NZB marrow had substan tial numbers of CFU-S, much greater than controls. This CFU-S potentia l was found primarily in the Lip 6(neg) Thy 1(neg) Lineage(neg) fracti onated marrow, suggesting that that population contained early progeni tor cells that had not yet differentiated into B lineage cells. Both r adioprotection and increased CFU-S were transmitted serially by bone m arrow from DBA/2 recipients of Thy 1(neg) Lineage(neg) NZB marrow to s econdary and tertiary (irradiated) DBA/2 recipients. Also serially tra nsplanted were precursors of antibody forming cells. These findings su ggest that NZB Thy 1(neg) Lineage (neg) marrow cells play a critical r ole in the development of the abnormal phenotype of NZB mice. However, because this probably is not a homogeneous population, additional wor k will be necessary to define the surface and molecular properties of the cell or cells within the NZB Thy 1(neg) Lineage (neg) marrow popul ation which serve as progenitors of the cells which mediate NZB diseas e. (C) 1994 Academic Press, Inc.