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*
Cancer Research Campaign, Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, United Kingdom;
Department of Medicine, University of Wales College of Medicine, Heath Park, Cardiff, United Kingdom; and
Department of Rheumatology, University of Birmingham, The Medical School, Birmingham, United Kingdom
Ligation of CD40 on the surface of B cells induces multiple
phenotypic effects, many of which are mimicked by the EBV latent
membrane protein 1 (LMP1) through its interaction with downstream
components of the CD40 signaling pathway. Because the effects of LMP1
have been most closely studied in human Burkitt Lymphoma (BL) cell
lines retaining a tumor biopsy-like phenotype in vitro, we have
examined the response of a panel of such lines to CD40 ligation. Two
distinct patterns of response were observed that were unrelated to the
surface level of CD40 or to the EBV genome status of the lines.
Following exposure to either CD40-specific mAbs or the soluble trimeric
ligand (sCD40L), high responder (HR) lines showed rapid aggregation,
activation of NF-
B, up-regulation of cell surface markers
ICAM-1/CD54 and Fas/CD95, and growth inhibition. Aggregation was seen
at lower doses than those required to elicit the other effects. By
contrast, low responder (LR) lines showed no detectable response to
CD40 mAbs, while their responses to sCD40L were limited to activation
of NF-B and up-regulation of CD95 only. However, in transfection
experiments, LMP1 uniformly induced the full spectrum of phenotypic
effects in both HR and LR lines. We conclude that some BL cell lines
show a highly restricted response to CD40 ligation but remain fully
susceptible to LMP1.
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