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B Is Required for Peptide Antigen-Induced Differentiation of a CD4+CD8+ Thymocyte Line1
*
Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852; and
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
NF-
B transcription factors are known to regulate the expression
of a number of genes involved in T cell activation and function. Some
evidence has suggested that they also play a role in T cell
development. However, the role of NF-B in Ag-induced thymocyte
differentiation has not been directly addressed to date. Here we
critically examine this role by employing DPK, a
CD4+CD8+ thymocyte line that undergoes
differentiation upon TCR engagement in a process that closely mimics
positive selection. Expression of a degradation-resistant form of
IB
in DPK cells results in constitutive inhibition of NF-B
activity. We find that in the absence of NF-B activity,
MHC-peptide-induced differentiation of DPK is blocked. Furthermore,
differentiation induced by a nonphysiologic stimulus, anti-TCR Ab,
is greatly reduced. Altogether, our data indicate a requirement for
NF-B in the developmental changes associated with positive
selection.
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