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Human B-cell interleukin-10: B-cell lines derived from patients with
acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively
secrete large quantities of interleukin-10 [see comments]
D Benjamin, TJ Knobloch and MA Dayton
Division of Hematology and Oncology, Arthur G. James Cancer Hospital and
Research Institute, Ohio State University, Columbus 43210-1228.
A recent addition to the lymphokine network is human IL-10 (hIL-10). This
novel lymphokine has striking homology to BCRF1 protein, the product of a
previously uncharacterized open-reading frame in the Epstein-Barr virus
(EBV) genome. To date, IL-10 expression has been described in several T
clones induced with anti-CD3 and phorbol myristate acetate (PMA), in
monocytes stimulated with lipopolysaccharide (LPS), and in murine B-cell
lymphomas. We sought to determine whether human B cells express hIL-10 and,
if so, its relationship to EBV and to other B-cell lymphokines. We studied
21 EBV- positive B-cell lines derived from patients with acquired
immunodeficiency syndrome (AIDS) and Burkitt's lymphoma (n = 6), American
Burkitt's (n = 3), African Burkitt's (n = 5), and normal lymphoblastoid
cell lines (n = 7), in comparison with seven EBV- negative cell lines. All
cell lines were activated with the tumor promoters PMA and teleocidin and
were studied by Northern blot analysis, reverse transcription-polymerase
chain reaction (RT-PCR), and enzyme-linked immunoadsorbent assay (ELISA).
We demonstrated that EBV- positive cell lines derived from patients with
American Burkitt's lymphoma, and especially those from patients with AIDS,
constitutively express large quantities of hIL-10 by Northern blot analysis
and ELISA (range, 3,101 to 25,915 pg/mL), and that both teleocidin and PMA
induce hIL-10 in these cell lines. In contrast, six of seven EBV-negative
cell lines did not express hIL-10 even by RT-PCR, and hIL-10 was not
triggered by PMA or teleocidin. To assure that the 350 bp amplified by PCR
was hIL-10 and not BCRF1, we used PCR primers, which do not amplify a
fragment from plasmid templates containing BCRF1. Cloning and sequencing of
the 350 bp product also demonstrated that B-cell IL-10 is identical to
hIL-10 from the T-cell clone B21. Correlation of hIL-10 with other B-cell
lymphokines secreted by these B-cell lines demonstrated that hIL-10
secretor cell lines also constitutively secrete or can be induced to
secrete IL-6, although to a much lesser amount. Since both lymphokines
influence B-cell growth and differentiation, we suggest that hIL-10 may
contribute to the polyclonal B-cell activation and hyperglobulinemia seen
in AIDS patients. Finally, several reports support the hypothesis that EBV
is an important cofactor in the development of human immunodeficiency virus
type 1 (HIV-1)-related B-cell lymphomas. Detection of large quantities of
hIL-10 in B-cell lines derived from AIDS patients, the close association
between EBV and hIL-10 shown in this report, and the ability of BCRF1 to
capture hIL-10 activities, make hIL-10/BCRF1 an attractive candidate as a
factor causing B-cell growth and immortalization in patients with AIDS and
B-cell lymphomas.
Volume 80,
Issue 5,
pp. 1289-1298,
09/01/1992
Copyright © 1992 by The American Society of Hematology

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