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Blood, 15 September 2000, Vol. 96, No. 6, pp. 2219-2225
NEOPLASIA
Soluble CD40 ligand induces selective proliferation of lymphoma
cells in primary mantle cell lymphoma cell cultures
Niels S. Andersen,
Jørgen
K. Larsen,
Jette Christiansen,
Lone B. Pedersen,
Nicolaj S. Christophersen,
Christian H. Geisler, and
Jesper Jurlander
From the Leukemia and Lymphoma Marker Laboratory,
Department of Hematology, and the Finsen Laboratory, Rigshospitalet,
Copenhagen, Denmark.
Interaction between CD40 and the CD40 ligand (CD40L) is critical
for the survival and proliferation of B cells during immunopoiesis. However, the role of CD40L in the pathogenesis of malignant lymphomas is ambiguous. Primary mantle cell lymphoma (MCL) cells were cultured in
the presence of recombinant human CD40L trimer (huCD40LT), and a
significant time- and dose-dependent induction of DNA synthesis was
observed in thymidine incorporation assays (n = 7,
P < .04). The maximal rate of DNA synthesis was reached
at huCD40LT doses of 100 ng/mL and above after 4 days of culture, but a
significant increase of DNA synthesis was detected already at doses of
1 ng/mL (P = .03). HuCD40LT never inhibited the basal
level of DNA synthesis. These findings established 400 ng/mL of
huCD40LT for 4 days as standard conditions in the system. Under
these conditions, huCD40LT significantly increased the proportion of
cells in the S/G2/M phases of the cell cycle in 4 of 7 studied cases, while the fraction of apoptotic cells remained unchanged
(n = 7). HuCD40LT also induced expression of CD80/B7-1, CD86/B7-2,
and CD95/Fas and up-regulated the expression of HLA-DR (n = 6). With
the use of bromodeoxyuridine incorporation in triple-color flow
cytometric analysis, it was found that huCD40LT induced cell-cycle
progression in light chain-restricted cells only, of which a median of
14% (range, 0.5% to 29%; n = 4) returned to G0/1 phase
DNA content after bromodeoxyuridine incorporation, demonstrating
completion of at least one cell cycle in the presence of huCD40LT.
Thus, primary clonal MCL cells are activated and can proliferate in the
presence of huCD40LT as a single agent.
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