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*
Department of Biology, College of Science, Yonsei University, Seoul, Korea;
Clon Biotech, Seoul, Korea; and
Department of Microbiology, Kangwon National University School of Medicine, Chunchon, Korea
Follicular dendritic cells (FDC)3 play crucial roles in
germinal center (GC) formation and differentiation of GC B cells. Many
aspects of FDC function are influenced by contact with B or T cells,
and by cytokines produced in the GC, which involve stimulation of CD40
and TNF-
receptors on FDC. In this study, using an established FDC
line, HK cells, we compared the effects of CD40 and TNF receptor
triggering on cytokine induction and activation of mitogen-activated
protein kinase family. We show that HK cells spontaneously produced
IL-6, M-CSF, and G-CSF mRNA. Both the soluble form of CD40 ligand
(sCD40L) and TNF increased the level of M-CSF and G-CSF mRNA. While TNF
strongly induced IL-6 mRNA, its expression was not affected by sCD40L
treatment, differing from the strong IL-6 induction in other cell types
upon CD40 stimulation. In addition, sCD40L treatment resulted in
activation of extracellular signal-related kinase 1 and 2 (ERK1/2) and
p38 without significant increase in c-Jun N-terminal kinase (JNK)
activity. Lack of JNK activation differs in that most B cells respond
to CD40 stimulation by inducing JNK activity strongly, suggesting
distinct characteristics of CD40 signaling in FDC. Compared with the
effects of sCD40L, TNF was capable of inducing JNK activity in addition
to the activation of ERK1/2 and p38. Furthermore, the proximal
signaling elements activated by TNF differed from those activated by
sCD40L, in that TNF did not require PMA-sensitive protein kinase C
isoforms in the activation of ERK and p38, whereas sCD40L did. However,
signals activated by these stimuli converged on cytokine gene
expression in a synergistic manner, which may have implication in
augmenting FDC function during GC reaction.
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