Evidence that immunoglobulin specificities of AIDS-related lymphoma are not directed to HIV-related antigens.
Chronic B-cell stimulation may be a predisposing event in the early pathogenesis of the acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL). ARL-derived immunoglobulin (Ig) genes are significantly diversified from germline, suggesting that antigenic stimulation via Ig receptors may occur prior to malignant transformation. We have evaluated 6 ARL-derived antibodies for binding to human immunodeficiency virus (HIV) and cell surface epitopes. Five cases expressed IgM, and 1 case expressed IgG. Expressed V genes were significantly diversified (3%-15%) from known germline V genes. A non-Ig producing mouse myeloma cell line was transfected with expression vectors containing the lymphoma-derived V genes. By enzyme-linked immunosorbent assay and Western blot assay, the lymphoma-derived Ig's showed no reactivity against HIV recombinant proteins. Also, no specific HIV reactivity was observed by flow cytometry with lymphoma-derived Ig's against the T-cell line infected with T-tropic HIV-1 or peripheral blood mononuclear cells infected with M-tropic HIV strains, indicating lack of binding to native HIV epitopes. However, 2 of the lymphoma-derived Ig's (ARL-7 and ARL-14) bound strongly to non-HIV-infected cells of various tissue origins. Thus, these findings suggest that the transformed B cells of AIDS-associated lymphomas may not arise from the pool of anti-HIV specific B cells but, rather, may develop from B cells responding to other antigens, including self-antigens. (Blood. 2000;95:1393-1399)
Cunto-Amesty
G
G
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
Przybylski
G
G
Honczarenko
M
M
Monroe
J G
JG
Silberstein
L E
LE
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000235:genetics; D000974:Antibodies, Antinuclear / Q000235:genetics; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000235:genetics*; D001323:Autoantibodies / Q000096:biosynthesis / Q000235:genetics; D003001:Cloning, Molecular; D005803:Genes, Immunoglobulin; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics*; D016483:Lymphoma, AIDS-Related / Q000276:immunology*; D051379:Mice; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D015488:HIV Antigens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D011994:Recombinant Proteins