Induction of human IgM and IgG anti-GM1 antibodies in transgenic mice in response to lipopolysaccharides from Campylobacter jejuni.
Campylobacter jejuni lipopolysaccharides (LPS) are implicated in the development of autoantibodies to GM1 ganglioside in patients with neuropathy following C. jejuni infection. CjLPS bears oligosaccharides that are cross reactive with GM1 ganglioside and presumably exerts its effects via molecular mimicry. To study the mechanisms that are involved in development of the autoantibody response, a transgenic mouse line was developed that expresses an IgM anti-GM1 antibody derived from a patient with multifocal motor neuropathy (MMN). In vivo stimulation of the transgenic mice with C. jejuni lipopolysaccharides (CjLPS), but not of wild-type mice readily elicited high serum titers of anti-GM1 IgM antibodies, followed by IgG anti-GM1 antibodies after two booster injections. In in vitro experiments, CjLPS stimulated the transgenic B-cells at lower concentration than control LPS. The increased sensitivity to CjLPS and the induction of IgG anti-GM1 by CjLPS but not control LPS are consistent with a mechanism of B-cell activation that involves both the LPS and the antigen-specific surface Ig receptors, with possible participation of T-cells.
Lee
Grace
G
Department of Neurology and Neuroscience, Weill Medical College, Cornell University, New York, NY, USA. GRL2003@med.cornell.edu
Jeong
Youngkee
Y
Wirguin
Itzik
I
Hays
Arthur P
AP
Willison
Hugh J
HJ
Latov
Norman
N
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D016123:Campylobacter jejuni / Q000276:immunology* / Q000302:isolation & purification; D005677:G(M1) Ganglioside / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D005677:G(M1) Ganglioside