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PM van Endert, B Heilig, GJ Hammerling and G Moldenhauer
Institute for Immunology and Genetics, German Cancer Research Center,
Heidelberg.
The effect of monoclonal antibodies (MoAbs) recognizing idiotype, IgM heavy
chain, and IgD heavy chain on the in vitro DNA synthesis of five randomly
selected leukemic human low-malignancy B-cell lymphomas was investigated.
In three lymphomas of different histologic subtype, low concentrations of
anti-idiotypic (anti-Id) MoAb completely inhibited spontaneous 3H-thymidine
uptake of T-cell-- and monocyte-depleted tumor cells, whereas two other
tumors were not affected. Maximal inhibition of DNA synthesis was achieved
at MoAb concentrations ranging from 0.5 to 250 micrograms/mL and required
crosslinking by bivalent antibody but not Fc-mediated effects. While two
anti-IgM MoAbs were similarly efficient as anti-Id MoAb in inhibition of
DNA synthesis, two anti-IgD MoAbs had no effect. Thus, surface IgD
molecules seemed to be neither able to deliver inhibitory signals
themselves nor to antagonize IgM- mediated signals when simultaneously
crosslinked by anti-Id MoAb. Leukocyte differentiation antigen expression,
IgM density, and IgM/IgD ratio on the surface of lymphoma cells did not
distinguish between sensitive and resistant tumors. In vitro tumor cell
survival was differently affected by prolonged incubation with anti-Id
antibody. In a centrocytic lymphoma and an immunocytoma, but not in a
chronic lymphocytic leukemia, suppression of 3H-thymidine uptake persisted
after removal of MoAb and tumor cell viability decreased during prolonged
incubation with anti-Id MoAb. These results suggest that direct inhibitory
signaling via surface IgM may contribute to anti-Id MoAb-mediated tumor
regression in certain human B-cell lymphomas.
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||