LYMPHOID CELLS IN PRODUCTION OF ANTIBODIES

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Recent experiments in this laboratory have established the rapid induction by IgD myeloma protein, IL-2 or IL-4, of receptors for IgD (IgD-R) on a large percentage of helper mouse T cells and T cell clones. This expression of IgD-R on CD4+ T cells results in augmentation of their helper activity for antibody production, demonstrable by cell transfer experiments. The upregulation of IgD-R expression with IgD and with IL-4 succeeds with cells from young adult, but not from aged mice, while IL-2 and several other agents are effective with cells from either population. Of particular interest is the preliminary finding that preincubation with a Ca++-ionophore renders T cells from aged mice responsive to IgD. The mechanism by which IgD causes upregulation of IgD-R on T cells will be investigated with respect to the need for protein and mRNA synthesis, glycosylation, intracellular changes in Ca++ levels, PKC activity and translocation in the cells, and activation of cyclic AMP and cyclic GMP dependent protein kinases. In addition, the pattern of phosphorylation of cellular proteins will be studied, with particular attention to autophosphorylation of the IgD-R itself. Any detectable effects of IgD on cells from young mice will be compared with effects on cells from aged mice. The possible relationship between cell membrane fluidity and responsiveness of T cell to IgD will be explored. Biochemical characteristics of IgD-R on cells from young and aged mice will be compared, as will the ability of the cells to release IgD-binding factors after stimulation. Conditions which cause upregulation of IgD-R on T cells from aged mice will be exploited in order to augment the defective helper T cell activity for antibody responses in these mice. Expression of surface antigens CD2, CD3, CD4, LFA1, and ICAM1, as well as of cytokine mRNA in T cells exposed to IgD, will be studied as an approach towards understanding the mechanism of the enhanced helper function of T-delta cells. Studies will be conducted on the effects of lifelong IgD administration on : a) the ability of T cells to express IgD-R beyond the age when control mice no longer respond, b) the level of the antibody responses, and c) longevity.