SYNERGISTIC AUGMENTATIVE EFFECT OF INTERLEUKIN-10 AND CD27 CD70 INTERACTIONS ON B-CELL IMMUNOGLOBULIN-SYNTHESIS/

Interleukin-10 (IL-10) is a potent cytokine that regulates immunoglobu lin synthesis by B cells. CD27/CD70 interactions by direct cell-to-cel l contact are also needed to produce substantial amounts of immunoglob ulin. We have investigated the effects of IL-10 and CD27/CD70 interact ions on the immunoglobulin synthesis. In the presence of IL-10 stimula tion, the production of IgG, IgM and IgA was increased synergistically by the addition of CD27 ligand (CD70)-transfectants in a dose-depende nt manner, which was completely blocked by anti-CD70 monoclonal antibo dy. In contrast, CD70-transfectants additively enhanced the immunoglob ulin production in the presence of IL-2, IL-4, or IL-6. The synergisti c enhancement of the immunoglobulin production by IL-10 and CD70-trans fectants was remarkable in highly purified CD27(+) B cells, but there was no immunoglobulin production in CD27(-) B cells. Furthermore, by t he addition of CD70-transfectants, the synthesis of IgG1, IgG2, IgG3 a nd IgG4 was also enhanced in the presence of IL-10. On the other hand, IL-10 diminished CD27 expression in B cells. B-cell proliferation was augmented by CD70-transfectants with IL-10 or IL-10 plus IL-2. The ad dition of IL-2 further augmented the immunoglobulin production which w as synergistically enhanced by IL-10 and CD27 triggering. Taken togeth er, the co-operative response to IL-10 and CD27/CD70 interactions regu lates B-cell immunoglobulin production.