Altered regulation of epstein‐barr virus induced lymphoblast proliferation in rheumatoid arthritis lymphoid cells

Abstract

Abstract An empiric observation of the rapid development of B lymphoblast cell lines after in vitro infection with Epstein‐Barr virus (EBV) in peripheral blood mononuclear cells (PBM) from patients with rheumatoid arthritis (RA) led us to compare cellular regulation of EBV‐induced lymphoblast outgrowth in RA and normal lymphoid cell populations. We found that RA PBM developed proliferating B lymphoblast colonies in a median time of 10 days after exposure to an EBV containing culture supernatant, while normal PBM took 18 days to grow out under the same conditions. The more rapid outgrowth of RA cells was not due to therapy with antiinflammatory or antirheumatic drugs. The time to outgrowth of the normal cells decreased to 11 days after T cell depletion. T cell depletion of the RA cells had less effect on the time to outgrowth but it was shortened to 8 days. B lymphoblast cell lines were established from “purified” T cell populations from 18 of 20 RA patients, while populations of T cells from normal donors with the same percentage of T and B cells did not produce lymphoblast cell lines when infected with EBV. In addition, we found that the non‐ T lymphoid cells from 7 of 20 RA patients established permanent B lymphoblast cell lines spontaneously without EBV infection. Spontaneous outgrowth of lymphoid cells from normal donors occurred only once in 48 experiments. These results indicate abnormalities in cell‐mediated regulation of EBV‐induced cell proliferation in lymphoid cells from patients with RA.