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-Barré 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 (5/15), predominance of IgM (9/15) or IgG3 (3/6) isotype, low affinity, and utilisation of unmutated VH and VL VDJ 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.
Boffey
Judith
J
University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland G51 4TF, UK.
Nicholl
Dawn
D
Wagner
Eric R
ER
Townson
Kate
K
Goodyear
Carl
C
Furukawa
Keiko
K
Furukawa
Koichi
K
Conner
Joe
J
Willison
Hugh J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000915:Antibody Affinity; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D016123:Campylobacter jejuni / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005732:Gangliosides / Q000235:genetics / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D018985:Epitopes, B-Lymphocyte; D005732:Gangliosides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D008070:Lipopolysaccharides