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 disorders can result in significant clinical improvement in some patients. The mechanism(s) by which IVIg induces these improvements is(are) not known. 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 cell line JY, whose proliferation was inhibited by IVIg, was incubated with IVIg, washed extensively with PBS, and lysed. Human IgG from these lysates was purified by protein A-Sepharose (IVIgJY). IVIgJY binds to and inhibits the proliferation of JY cells and of peripheral blood lymphocytes stimulated in a MLR at a 1000- to 10,000-fold lower concentration compared to IVIg. IVIgJY was analyzed on a 5-15% gradient SDS/PAGE and only immunoglobulin heavy- and light-chain (run under reducing conditions) proteins were detected. Immunoprecipitation experiments from JY cell lysates with IVIgJY indicated that this IgG did not bind to a protein epitope. Thin-layer immunoblot experiments showed that the IVIgJY binds to glycolipids expressed by JY cells and lymphocytes. Furthermore, evidence is presented indicating that antiglycolipid antibodies are involved in IVIg-induced growth inhibition.
Vuist
W M
WM
Department of Immunohematology and Bloodbank, Academical Hospital Leiden, The Netherlands.
Van Schaik
I N
IN
Van Lint
M
M
Brand
A
A
D000906:Antibodies / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000276:immunology; D006017:Glycolipids / Q000276:immunology*; D006131:Growth Inhibitors / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology; D008563:Membrane Lipids / Q000276:immunology*
D000906:Antibodies; D006017:Glycolipids; D006131:Growth Inhibitors; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008563:Membrane Lipids