Regulation of IgM rheumatoid factor production in lymphocyte cultures from young and old subjects

Sera from 31 healthy donors over age 70 had significantly higher levels of IgM rheumatoid factor, measured by radioimmunoassay, than sera from 27 young controls (25,400 ± 7867 ng/ml vs 2644 ± 347 ng/ml, mean ± SEM, p<0.0001). Pokeweed mitogen-stimulated peripheral blood lymphocytes from healthy donors over age 70 also produced significantly higher amounts of IgM-rheumatoid factor 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). We investigated the control of IgM RF production by performing co-culture 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 cells subjects were isolated using the monoclonal antibodies OKT4 and OKT8, we demonstrated an increased helper activity of OKT4(+) cells from old subjects, whereas 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 addition, 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.