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Evidence for early B-cell activation preceding the development of
Epstein-Barr virus-negative acquired immunodeficiency syndrome-related
lymphoma
GK Przybylski, J Goldman, VL Ng, MS McGrath, BG Herndier, DP Schenkein, JG Monroe and LE Silberstein
Department of Pathology and Laboratory Medicine, University of Pennsylvania
Medical Center, Philadelphia 19104-6082, USA.
To investigate the origin and pathogenesis of acquired immunodeficiency
syndrome (AIDS)-related lymphoma (ARL), we studied 14 cases in which
Epstein-Barr virus (EBV) infection was not an etiologic factor. By
histology, 8 of the specimens were of the small noncleaved cell type and 6
consisted of the large diffuse cell type. Southern analysis using a J(H)
probe was consistent with a monoclonal B-cell tumor in 13 cases. To
characterize the expressed Ig genes, we performed reverse
transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing of
PCR products. Eight cases expressed IgM and 1 case expressed IgG. V(H)3
genes were found in 5 cases, V(H)4 genes in 3 cases, V(H)1 genes in 2
cases, and a V(H)7 gene in 1 case. The nucleotide homology to known
germline V(H) genes ranged from 80% to 97%, suggesting significant somatic
diversification of expressed V(H) genes. The large proportion of
V(H)3-expressing lymphomas in this series corresponds to the frequency of
V(H)3-expressing B cells in the peripheral blood from healthy and (recent)
human immunodeficiency virus (HIV)-seropositve individuals and contrasts
with the V(H)3 clonal deficit observed in late stages of HIV infection.
Similar to the Ig heavy chain genes, the corresponding Ig light chain genes
showed significant deviation from known germline gene sequences. The large
proportion of V(H)3-expressing lymphomas as well as the high degree of
somatic deviation from germline suggest that these EBV-negative lymphomas
might arise from antigen- selected expanded B-cell clones before
transformation. Further support for this hypothesis is provided by
sequential Ig sequence analysis in 1 patient with large-cell lymphoma. It
was shown that 3 years before the diagnosis of axillary lymphoma, there
existed several B-cell clones in this patient's bone marrow. One of these
clones present in the bone marrow expressed the same rearranged V(H) gene
as the axillary lymphoma. Taken together, the current findings from Ig gene
analyses suggest that activation of B cells in the early phase of HIV
infection may be a predisposing factor for subsequent B-cell
transformation.
Volume 88,
Issue 12,
pp. 4620-4629,
12/15/1996
Copyright © 1996 by The American Society of Hematology
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