The Journal of Immunology, Vol 149, Issue 7 2518-2529, Copyright © 1992 by American Association of Immunologists

ARTICLES

Structure and specificities of anti-ganglioside autoantibodies associated with motor neuropathies

NP Weng, LY Yu-Lee, I Sanz, BM Patten and DM Marcus
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.

Autoantibodies that bind to GM1 ganglioside and asialo GM1 (GA1) have been implicated in the pathogenesis of motor neuropathies. To investigate the structure and specificity of these autoantibodies, peripheral blood B cells from patients with motor neuron diseases and from normal individuals were immortalized by EBV, and B cells secreting anti-GM1 or GA1 antibodies were cloned. We report an analysis of the structure and specificities of eight autoantibodies from patients with motor neuropathy, and two from normal individuals. Four antibodies were IgM, six were IgG, and all bound predominantly to GA1. The sequences of V domains of H and L chains were determined by a reverse transcription- polymerase chain reaction procedure. A variety of V genes were used to encode these antibodies: four VH1, two VH3, three VH4, one VH5, two V kappa I, two V kappa II, three V kappa III, and two V lambda II. Most V genes (13/19) exhibited less than 95% similarity to known germ-line genes, which suggests that somatic mutation was required to generate these autoantibodies, or that the relevant germ-line genes have not been identified. The average length of the H chain CDR3 was 16 amino acids, and in three antibodies this segment contained more than 20 amino acids. It was not possible to identify amino acid sequences that were encoded by germ-line D segments by conventional alignment of sequences. Partial analogies could be identified by introducing gaps, allowing mismatches and searching for D-D fusions and inversions. These results indicate that anti-GA1 antibodies can be encoded by a variety of VH-VL pairs, that the antibodies exhibit extensive somatic mutation, and that the CDR3 segments are generated by a number of nonconventional mechanisms.

This article has been cited by other articles:

				C. A. Kirvan, C. J. Cox, S. E. Swedo, and M. W. Cunningham Tubulin Is a Neuronal Target of Autoantibodies in Sydenham's Chorea J. Immunol., June 1, 2007; 178(11): 7412 - 7421. [Abstract] [Full Text] [PDF]

				A. H. Lucas, K. D. Moulton, V. R. Tang, and D. C. Reason Combinatorial Library Cloning of Human Antibodies to Streptococcus pneumoniae Capsular Polysaccharides: Variable Region Primary Structures and Evidence for Somatic Mutation of Fab Fragments Specific for Capsular Serotypes 6B, 14, and 23F Infect. Immun., February 1, 2001; 69(2): 853 - 864. [Abstract] [Full Text] [PDF]

				R. H. Quarles The Spectrum and Pathogenesis of Antibody-mediated Neuropathies Neuroscientist, May 1, 1997; 3(3): 195 - 204. [Abstract] [PDF]

				G. Boucher, H. Broly, and R. Lemieux Restricted Use of Cationic Germline VH Gene Segments in Human Rh(D) Red Cell Antibodies Blood, May 1, 1997; 89(9): 3277 - 3286. [Abstract] [Full Text] [PDF]