The effect of aging on the immune response: influence of phosphatidylcholine-containing lipid on IgD-receptor expression and antibody formation.
It was reported previously that IgD-receptors (IgD-R) are expressed on both CD4+ and CD8+ human T cells and CD4+ murine T cells after exposure to oligomeric IgD, certain cytokines, or various pharmacological agents, as shown by rosetting with IgD-coated erythrocytes. Enhancement of antibody production is observed in mice after injection of oligomeric IgD and is mediated by these IgD-R+ T cells, while injection of monomeric IgD inhibits both IgD-R upregulation and augmentation of antibody responses induced by simultaneously injected oligomeric IgD. The effects of oligomeric IgD on IgD-R upregulation are lacking in aged mice. However, the oligomeric IgD induced enhanced antibody production can be transferred to aged mice with IgD-R+ T cells from young donors suggesting that the environment of the aged mouse supports the effector function of IgD-R+ T cells. We now report, in addition, that exposure to phosphatidylcholine (PC) and a PC-containing lipid mixture, AL721, is effective in causing IgD-R upregulation on T cells from both young and aged mice, and young humans. This effect can also be demonstrated in mice in vivo after administration of AL721. Moreover, this agent causes a two-fold enhancement of antibody production, as measured by PFC/spleen, to 4-hydroxy-5-iodo-3-nitrophenyl(acetyl)-Brucella abortus (NIP-BA) and NIP-horse red blood cells (RBC) in young and aged mice. There is no difference in the baseline membrane fluidity of lymphocytes from aged and young mice. Although PC causes an increase in membrane fluidity of lymphocytes from both young and old mice, and from humans, this effect on fluidity is not prevented by a protein kinase inhibitor, while PC's effect on IgD-R upregulation is prevented by the inhibitor. Moreover, no correlation was observed between IgD-R upregulation and membrane fluidity changes induced by AL721 administered in vivo. To evaluate the role of IgD-R induction in the augmentation of antibody production by phospholipids, the effect of monomeric IgD was investigated. The augmenting effect of AL721 on antibody production was prevented by a single injection of monomeric IgD at the time of antigen administration. We conclude that (1) PC-containing lipid mixtures are effective in enhancing antibody production in aged mice, (2) induction of IgD-R is responsible for the augmenting effects of AL721 on antibody production, and (3) monomeric IgD not only blocks the upregulation of IgD-R, as shown previously, but also the augmenting effect of previously upregulated IgD-R on T cells by preventing their interaction with surface IgD+ B cells.
Swenson
C D
CD
Department of Pathology, New York University School of Medicine, NY 10016, USA.
Gottesman
S R
SR
Xue
B
B
Edington
J
J
Thorbecke
G J
GJ
D000375:Aging / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003430:Cross-Sectional Studies; D004333:Drug Administration Routes; D006801:Humans; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010713:Phosphatidylcholines / Q000494:pharmacology*; D011961:Receptors, Fc / Q000187:drug effects*; D019311:Staurosporine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*; D016378:Tissue Transplantation / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
D007072:Immunoglobulin D; D010713:Phosphatidylcholines; D011961:Receptors, Fc; D019311:Staurosporine