Regulation of immunoglobulin production in pokeweed mitogen-stimulated cultures of lymphocytes from young and old adults
Ceuppens, J.L.; Goodwin, J.S.
Journal of Immunology 128(6): 2429-2434
1982
ISSN/ISBN: 0022-1767 PMID: 6210731 Document Number: 183112
Polyclonal (pokeweed mitogen-stimulated) humoral immune responses were studied in cultures of peripheral blood mononuclear cells or T + B cell combinations of young (20-40 yr) and aged (> 65 yr) individuals. (Ig) production was measured in the culture supernatants with an enzyme-linked immunosorbent assay 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. Isolated OKT4(+) cells of old people provided more help than OKT4(+) cells of young people; 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. 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 substantially less IgM than young B cells did (1010 .+-. 240 vs. 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 erythrocyte 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; 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. Increased helper and decreased suppressor activity of isolated T cell subpopulations was found from healthy elderly individuals; 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.