IgG Subclasses and Isotypes of VH4-34 Encoded Antibodies.
VH4-34 gene encoded autoantibodies are elevated in systemic lupus erythematosus (SLE) and in other diseases associated with B-cell hyperproliferation/dysfunction. One of the autoantigens recognized by VH4-34-encoded antibodies are branched/linear poly N-acetyl lactosamine chains. Since the anti-carbohydrate response in humans is dominated by the IgG2 subclass, here we tested whether VH4-34 encoded IgG showed similar subclass segregation. Serum samples from SLE, infectious mononucleosis, nasopharyngeal carcinoma and hepatitis-C were analyzed. Levels of VH4-34-encoded IgM and IgA isotypes were also tested. VH4-34-IgM and IgA were elevated in all four clinical conditions. VH4-34-IgG was detected in the IgG1 and IgG3 subclass but not in the IgG2 and IgG4 subclass. Interestingly, VH4-34-IgG3 was also detected in serum samples of normal healthy adults. These observations are discussed in context of the VH4-34 gene regulation. VH4-34 repertoire development is of interest since it is the only human VH gene profoundly overrepresented in the naïve repertoire but counter-selected for antibody secretion. VH4-34 B-cell could thus become a unique tool to inspect germinal center independent/dependent pathways of subclass and isotype-specific antibody secretion.
Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Stanford University School of Medicine , Stanford, California , USA.
Neelima M
NM
Bhat
Mihir A
MA
Kshirsagar
Marcia M
MM
Bieber
Nelson N H
NN
Teng
D001323:Autoantibodies / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008297:Male; D010641:Phenotype
D001323:Autoantibodies; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M
9G4; HCV; IM; SLE; autoantibodies