THE GROWTH ARRESTING EFFECT OF HUMAN-IMMUNOGLOBULIN FOR INTRAVENOUS USE IS MEDIATED BY ANTIBODIES RECOGNIZING MEMBRANE GLYCOLIPIDS

Intravenous human IgG (IVIg) given to patients with autoimmune disorde rs can result in significant clinical improvement in some patients. Th e mechanism(s) by which IVIg induces these improvements is(are) not kn own. We have previously shown that IVIg inhibited the proliferation of peripheral blood lymphocytes in allogeneic mixed lymphocyte reactions and of autonomously growing human and mouse cell lines. In an effort to identify the antigen(s) to which the human IgG binds, the human B c ell line JY, whose proliferation was inhibited by IVIg, was incubated with IVIg, washed extensively with PBS, and lysed. Human IgG from thes e lysates was purified by protein A-Sepharose (IVIg(JY)). IVIg(JY) bin ds to and inhibits the proliferation of JY cells and of peripheral blo od lymphocytes stimulated in a MLR at a 1000- to 10.000-fold lower con centration compared to IVIg. IVIg(JY) was analyzed on a 5-15% gradient SDS/PAGE and only immunoglobulin heavy- and light-chain (run under re ducing conditions) proteins were detected. Immunoprecipitation experim ents from JY cell lysates with IVIg(JY) indicated that this IgG did no t bind to a protein epitope. Thin-layer immunoblot experiments showed that the IVIg(JY) binds to glycolipids expressed by JY cells and lymph ocytes. Furthermore, evidence is presented indicating that antiglycoli pid antibodies are involved in IVIg-induced growth inhibition.