Aberrant expression of GM1 on lymph node cells of MRL/Mp-lpr/lpr mice: influences on the autoreactivities of anti-asialo GM1 antibodies.
Although changes in surface carbohydrate expression of abnormally expanded MRL/Mp-lpr/lpr (MRL/lpr) lymph node (LN) cells have previously been described, the composition and function of glycolipids present on these cells as well as the spectrum of specificity of anti-carbohydrate antibodies reactive with these cells remains obscure. Analysis of antibodies to a panel of 22 carbohydrate structures using a liposome immune lysis assay (LILA) showed that, except for anti-asialo GM2 (GA2) antibodies, marked reduction of antiglycolipid antibody levels was observed in sera from 4-mo-old MRL/lpr mice compared with these from MRL/Mp(-)+/+ (MRL/+) mice. Absorption experiments revealed that both anti-asialo GM1 (GA1) and globoside antibodies had binding capacity to MRL/lpr LN cells. To elucidate the glycolipid profiles of MRL/lpr LN cells, glycolipids were extracted from LN cells of both MRL/lpr and MRL/+ mice and analysed. A 30-fold elevation of GM1 was found in MRL/lpr LN cells compared with MRL/+ LN cells. From the results of LILA using GA1/GM1 mixed liposomes, aberrantly expressed GM1 inhibited the classical complement pathway but did not interfere with the binding of anti-GA1 antibodies to liposomal GA1. These findings suggest that a drastic GM1 increase on MRL/lpr LN cells would inhibit the action of anti-GA1 antibodies and complement on the cell surface. This may explain the escape of these cells from an activated self directed immune response.
Ishii
N
N
Division of Immunology, Shigei Medical Research Institute, Okayama, Japan.
Watanabe
K
K
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D002240:Carbohydrate Sequence; D003165:Complement System Proteins / Q000276:immunology; D005677:G(M1) Ganglioside / Q000032:analysis* / Q000276:immunology*; D006017:Glycolipids / Q000737:chemistry / Q000276:immunology; D008081:Liposomes; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology*; D008817:Mice, Mutant Strains / Q000276:immunology*; D008969:Molecular Sequence Data
D001323:Autoantibodies; D006017:Glycolipids; D008081:Liposomes; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D003165:Complement System Proteins