Neutral proteinases induce rheumatoid factor production in mouse spleen cell cultures

Mouse spleen cells were cultured for 4 days in RPMI 1640 medium with 5% fetal calf serum. The neutral proteinases trypsin and plasmin, and bacterial lipopolysaccharide LPS, all polyclonal B lymphocyte activators, stimulated the development of immunoglobulin producing cells as detected by the protein A plaque assay. At the same time, direct plaque forming cells reacting with mouse, human and rabbit IgG and the Fc fragment of human IgG were induced by the stimulants. The plaques could be inhibited by free IgG or Fc fragment. In the culture supernatants, IgM and IgM anti-IgG antibodies were detected by enzyme linked immunosorbent assays. Both general IgM and IgM anti-IgG antibodies increased under the influence of the proteinases and of LPS. The results are discussed in relation to rheumatoid factor production during inflammatory diseases.