SPECIFICITY AND STRUCTURE OF MURINE MONOCLONAL-ANTIBODIES AGAINST GM1GANGLIOSIDE

Anti-GM1 antibodies have been implicated in the pathogenesis of severa l neurological diseases, but the role of these antibodies is still con troversial. An animal model could provide insight into the mechanisms of these human disorders, but obtaining specific anti-GM1 monoclonal a ntibodies (mAbs) has been extremely difficult because of the weak immu nogenicity of GM1 ganglioside. Four murine mAbs against GM1 were elici ted by immunization of mice with lyse GM1 coupled to BSA and GM1 glyco lipid. All four IgM,k mAbs bound strongly to GM1, three antibodies (12 5, 360 and 494) also bound very weakly to asialo GM1(GA1) and one (156 ) bound weakly to GD1b. Three antibodies (125, 360 and 494) were encod ed by the same V-H and V-kappa genes. The V-H gene exhibited 97% homol ogy to V(H)OX1, a member of the V(H)Q52N gene family, the D segment wa s probably derived from DQ52 and J(H) was identical to J(H)2. The V-ka ppa gene was approximately 99% homologous to V(kappa)RF and J(kappa) w as germline J(kappa)2. The V-H gene of mAb 156 exhibited 98% homology to V(H)205.12, of the V(H)J558 gene family, the D segment was derived from DFL16.1, and J(H) was germline J(H)2. The V-kappa and J(kappa) ge nes of mAb 156 were identical to V(kappa)8 and J(kappa)1, respectively . The genes encoding these anti-GM1 antibodies were close to germline sequences and have been used to encode other antibodies. This suggests that the unresponsiveness of mice to immunization is probably due to inactivation of self-reactive B cells. These rare anti-GM1 mAbs will b e valuable reagents for studies of the pathogenesis of autoimmune neur opathy in animals, and also for analyzing the tissue distribution and functions of GM1.