Innate murine B cells produce anti-disialosyl antibodies reactive with Campylobacter jejuni LPS and gangliosides that are polyreactive and encoded by a restricted set of unmutated V genes

In Guillain-Barre syndrome following Campylobacter enteritis, anti-lipopolysaccharide antibodies cross-react with neural gangliosides, thereby precipitating autoimmune neuropathy. We examined the properties of 15 murine anti-LPS/ganglioside mAbs specific for NeuAc(alpha2-8)NeuAc-Gal disialosyl epitopes. Many mAbs displayed features of an innate B cell origin including polyreactivity (13/15), hybridoma CD5 mRNA expression (5115), predominance of IgM (9/15) or IgG3 (3/6) isotype, low affinity, and utilisation of unmutated V-H and V-L V(D)J rearrangements. Antibody specificity resided in highly selective V gene usage, with 6/15 mAbs being encoded by the VH7183.3b gene. These data indicate that neuropathogenic antiganglioside autoantibodies can arise from the natural autoantibody repertoire. (C) 2004 Elsevier B.V. All rights reserved.