Regulation of immunoglobulin production in pokeweed mitogen-stimulated cultures of lymphocytes from young and old adults

Polyclonal (pokeweed mitogen-stimulated) humoral immune responses were studied in cultures of peripheral blood mononuclear cells (PBMC) or T + B cell combinations of young (20 to 40 yr) and aged (>65 yr) individuals. Immunoglobulin (Ig) production was measured in the culture supernatants with an ELISA method. Cultures of lymphocytes from old and young individuals produced similar amounts of IgG and IgM. In co-culture experiments of old or young B cells with old or young T cells, the old T cells consistently provided more help for old and young B cells than the young T cells did. In addition, isolated OKT4(+) cells of old people provided more help than OKT4(+) cells of young people, whereas the suppressor activity of isolated OKT8(+) cells from old people was diminished. Because young or old T cells induced less Ig production in old B cells than in young B cells, an intrinsic defect in the B cell function may also be present. Indeed, when B cell preparations from young and old subjects were cultured with soluble helper factors but without T cells or monocytes, old B cells produced substantiallly less IgM than young B cells did (1010 ± 240 versus 240 ± 64 ng/ml, mean ± SE, p < 0.01). Cell marker analysis on monocyte-depleted lymphocytes was carried out on a fluorescence-activated cell sorter (FACS). The proportion of B cells was slightly reduced in lymphocytes of old vs young donors. The proportions of E rosette(+) cells (reacting with Ab 9.6), of mature T cells (reacting with OKT1 and OKT3), and of helper inducer T cells (reacting with OKT4) were also decreased, whereas the proportions of suppressor T cells (reacting with OKT8 and of OKM1(+) null cells were increased. These quantitative changes in T cell subpopulations could partly balance the increase in helper and decrease in suppressor T cell function found in the isolated subpopulations. In sum, we have found increased helper and decreased suppressor activity of isolated T cell subpopulations from healthy elderly individuals, whereas total IgM and IgM production of lymphocyte cultures from old and young subjects was the same. The changes in helper and suppressor function may represent a homeostatic mechanism to maintain Ig production in the face of failing intrinsic B cell function with age.