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B Activation
*
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Lausanne, Switzerland; and
Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland
We introduce a new experimental system combining
adenovirus-mediated gene transfer and fetal thymic organ culture
(FTOC). This system allowed us to efficiently express in developing
thymocytes a mutant form of the NF-
B inhibitor IB
(mut-IB)
and to study the maturation defects occurring when NF-B activation
is inhibited during fetal development. Fetal thymocytes infected with
adenovirus containing mut-IB were found to develop normally until
the CD44-CD25+,
CD4-CD8- double-negative stage, while
production of more mature double-positive and single-positive
populations was strongly decreased. Proliferation, as measured by the
percentage of cells in cycle appeared normal, as did rearrangement and
expression of the TCR ß-chain. However, apoptosis was much higher in
FTOC infected with adenovirus containing mut-IB than in FTOC
infected with a control virus. Taken together, these results suggest
that NF-B plays a crucial role in ensuring the differentiation and
survival of thymocytes in the early stages of their
development.
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