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Responsiveness of chronic lymphocytic leukemia B cells activated via
surface Igs or CD40 to B-cell tropic factors
AC Fluckiger, JF Rossi, A Bussel, P Bryon, J Banchereau and T Defrance
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
Recent studies performed in the laboratory have established that
interleukin-4 (IL-4) used in combination with anti-CD40 monoclonal antibody
(MoAb) 89 presented on Ltk- mouse fibroblasts stably expressing human Fc
gamma RII/CDw32 (referred to as the CD40 system) sustains long-term
proliferation of normal human B cells. In the present study, B-cell chronic
lymphocytic leukemias (B-CLLs) activated through slgs or CD40 were examined
for their capacity to proliferate and differentiate in response to various
cytokines. Our results indicate that the outcome of IL-4 stimulation on the
in vitro growth of B-CLL depends on the signalling pathway used for their
activation. Whereas IL-4 did not display any growth-stimulatory effect on
B-CLL activated by Ig cross-linking agents, it could stimulate DNA
synthesis and enhance the viable cell recovery when leukemic B cells were
cultured in the CD40 system. Most B-CLL samples were induced for IgM
synthesis upon Staphylococcus aureus strain Cowan I stimulation. This Ig
response was potentiated by IL-2 and antagonized by IL-4. Anti-CD40 MoAb
used alone or in combination with cytokines (IL-1 alpha to IL-6, interferon
gamma, tumor necrosis factor gamma, and transforming growth factor beta)
failed to induce Ig secretion from B-CLL cells. No evidence for Ig isotype
switching was obtained with the cytokines listed above, regardless of the
mode of activation. Taken together, our results suggest that B-CLL cells
can be partially released from their apparent maturation block by IL-2 and
Ig cross-linking agents. In contrast, combinations of IL-4 and cross-linked
anti-CD40 antibodies induced entry of B-CLL cell into cycle, but poorly
stimulated their differentiation into Ig secreting cells.
Volume 80,
Issue 12,
pp. 3173-3181,
12/15/1992
Copyright © 1992 by The American Society of Hematology
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