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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2830-2843
Prolonged Phenotypic, Functional, and Molecular Change in Group I
Burkitt Lymphoma Cells on Short-Term Exposure to CD40 Ligand
Matthew P. Baker,
Aristides G. Eliopoulos,
Lawrence S. Young,
Richard J. Armitage,
Christopher D. Gregory, and
John Gordon
From the Departments of Immunology and the Institute of Cancer
Studies, University of Birmingham, Birmingham, UK; and Immunex Corp,
Seattle, WA.
Group I Burkitt lymphoma (BL) cell lines (L3055, Elijah, Louckes,
BL2, and BL29) retaining the original biopsy phenotype were found to
undergo prolonged phenotypic, functional, and molecular change on
short-term exposure to soluble recombinant CD40L trimer. Sensitivity
to, extent of, and duration of change appeared to reflect passage
number in that the earliest passaged lines, L3055 and BL29, were
generally the most susceptible. Culture of group I BL lines with CD40L
resulted in significant growth arrest (without apoptosis) that, for
L3055 cells, was sustained for 7 to 9 days after 72 hours of exposure.
This was accompanied by the formation of large homotypic aggregates
together with gross changes in individual cell morphology and a
concomitant upregulation of CD54 (ICAM-1). Three of the five group I BL
lines exhibited rapid downregulation of the hallmark CD77 surface
antigen, which, for L3055 cells, was maintained for at least 12 days
after 72 hours of incubation with CD40L. With the exception of BL2, all
group I BL lines were induced to express CD40 homodimers on
CD40-stimulation, whereas only monomers were detected in unstimulated
cells. Experiments using CD40-transfected Rat-1 fibroblasts showed that
the ability to signal for dimer formation required Thr234
of CD40. For L3055 and BL29 cells, an initial 72 hours of exposure to
CD40L resulted in the maintenance of homodimers for up to 14 and 10 days, respectively. There was a close correlation between the induction
and duration of CD40 homodimers and the appearance of Bcl-2. For L3055
cells, which are sensitive to apoptosis-induction on BCR-engagement,
exposure to CD40L for 72 hours was found to provide considerable
protection from anti-IgM, which was still significant to 20 days. The
implications of such sustained effects on relatively short-term
exposure of tumor B cells to CD40L are discussed.
© 1998 by The American Society of Hematology.
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