CLONING OF HUMAN ANTI-GM1 ANTIBODIES FROM MOTOR NEUROPATHY PATIENTS

Patients with multifocal motor neuropathy frequently have elevated tit ers of serum antibodies reactive with GM1 ganglioside. Although these antibodies may cause the syndrome, this has yet to be proven directly. As part of out studies on the nature and pathogenic potential of anti -GM1 antibodies, we have cloned B cells from the peripheral blood of 3 patients with multifocal motor neuropathy and generated four stable h eterohybridoma cell lines secreting human monoclonal IgM anti-GM1 anti bodies. In this report we describe the basic properties of these monoc lonal antibodies in comparison with the patient's sera from which they were derived. The antibodies all differ in their pattern of reactivit y with GM1 and other Gal(beta 1-3)GalNAc-containing glycoconjugates. T hey have widely varying thermal ranges and their reactivities are stro ngly influenced by the presence of accessory lipids. Affinity purifica tion of the patient's sera with GM1 led to the identification of previ ously unrecognized paraproteins that were resolvable above the backgro und of polyclonal anti-GM1 IgM. Our data demonstrate considerable hete rogeneity in the immune response to GM1 both within individual sera an d between different patients, which is likely to be of importance to t heir role in disease pathogenesis.