Regulation of IgM rheumatoid factor production in lymphocyte cultures from young and old subjects
Rodriguez, M.A.; Ceuppens, J.L.; Goodwin, J.S.
Journal of Immunology 128(6): 2422-2428
1982
ISSN/ISBN: 0022-1767 PMID: 6210730 Document Number: 183079
Sera from 31 healthy donors over age 70 had significantly higher levels of IgM rheumatoid factor [RF], measured by radioimmunoassay, than sera from 27 young controls (25,400 .+-. 7867 ng/ml vs. 2644 .+-. 347 ng/ml, mean .+-. standard error of the mean P < 0.0001). Pokeweed mitogen-stimulated peripheral blood lymphocytes from healthy donors over age 70 also produced significantly higher amounts of IgM-RF in vitro than lymphocytes from young controls. For individuals over 70, there was a significant correlation between levels of IgM RF in the sera and the levels produced in vitro (r = 0.43, P = 0.02). The control of IgM RF production was investigated by performing coculture experiments of B cells with either T cells or T cell subsets from subjects over 70 and young controls. T cells from old individuals provided more help than T cells from young individuals to B cells from either young or old individuals. When helper and suppressor T cell subjects were isolated using the monoclonal antibodies OKT4 and OKT8, increased helper activity of OKT4(+) cells from old subjects, was demonstrated; the suppressor activity of OKT8(+) cells did not differ between old and young subjects. In contrast to increased helper T cell activity, it appeared that B cells from old subjects were less capable of rheumatoid factor production than B cells from young controls given the same stimulus. B cells from young individuals produce more IgM-RF than B cells of subjects over 70 in the presence of T cells from subjects over 70 (92 .+-. 52 vs. 31 .+-. 54, P = 0.04) or in the presence of OKT4(+) T cells from either young or old donors. In experiments using enriched B cell preparations cultured with helper factor supernatants but without T cells, the B cells from young subjects produced significantly more rheumatoid factor than B cells from old subjects (P < 0.01). Thus, the increased IgM-RF production by old lymphocytes is due to an altered functional state in the old T cell population; the old B cells are actually less capable than young B cells of producing IgM-RF, given the same T cell help or helper factor. These results are consistent with a primary failure of B cell function with age with a resultant homeostatic increase in T helper cell function.