Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1393-1399
Evidence that immunoglobulin specificities of AIDS-related
lymphoma are not directed to HIV-related antigens
Gina Cunto-Amesty,
Grzegorz Przybylski,
Marek Honczarenko,
John G. Monroe, and
Leslie E. Silberstein
From the Department of Pathology and Laboratory Medicine, University
of Pennsylvania School of Medicine, Philadelphia, PA, and the Institute
of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
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.
