Bone marrow CD34(+) progenitor cells from rheumatoid arthritis patients support spontaneous transformation of peripheral blood B cells from healthy individuals

We show that bone marrow (BM) CD34(+) progenitor cells from rheumatoid arth ritis (RA) patients have the capacity to support spontaneous transformation of peripheral blood B cells. CD34(+) cells purified from BM blood from eig ht RA patients and eight osteoarthritis (OA) patients were expanded with gr anulocyte/macrophage colony stimulating factor (GM-CSF) for 4-6 weeks. GM-C SF-stimulated BM CD34(+) cells from three of eight RA patients, but none fr om seven OA patients, gave rise to spontaneous transformation of highly pur ified B cells of Epstein-Barr virus (EBV)-seronegative healthy donors. GM-C SF-stimulated BM CD34(+) cells from four of six RA patients and from one of four OA patients also supported the spontaneous transformation of peripher al blood B cells from EBV-seropositive healthy donors. All the transformed B cell lines were positive for EBV-DNA as determined by PCR. Neither GM-CSF -stimulated BM CD34(+) cells alone nor highly purified B cells alone gave r ise to spontaneously transformed B cell lines. These results suggest that t he capacity of BM CD34(+) cells to support survival of B cells might contri bute to the pathogenesis of RA by sustaining abnormal B cell responses.