The Journal of Experimental Medicine
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Published 22 January 2002. doi:10.1084/jem.20011885
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© Rockefeller University Press, 0022-1007/2002/1/233/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 2, January 21, 2002 233-244

Original Article

 Requirement for the NF-{kappa}B Family Member RelA in the Development of Secondary Lymphoid Organs

Elizabeth Alcamo1, Nir Hacohen2, Leah C. Schulte2, Paul D. Rennert3, Richard O. Hynes1 and David Baltimore4

1 Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
2 Whitehead Institute, Cambridge, MA 02142
3 Biogen Inc., Cambridge, MA 02142
4 California Institute of Technology, Pasadena, CA 91125

Address correspondence to Dr. Nir Hacohen, Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142. Phone: 617-258-9205; Fax: 617-258-5578; E-mail: hacohen{at}wi.mit.edu

The transcription factor nuclear factor (NF)-{kappa}B has been suggested to be a key mediator of the development of lymph nodes and Peyer's patches. However, targeted deletion of NF-{kappa}B/ Rel family members has not yet corroborated such a function. Here we report that when mice lacking the RelA subunit of NF-{kappa}B are brought to term by breeding onto a tumor necrosis factor receptor (TNFR)1-deficient background, the mice that are born lack lymph nodes, Peyer's patches, and an organized splenic microarchitecture, and have a profound defect in T cell–dependent antigen responses. Analyses of TNFR1/RelA-deficient embryonic tissues and of radiation chimeras suggest that the dependence on RelA is manifest not in hematopoietic cells but rather in radioresistant stromal cells needed for the development of secondary lymphoid organs.

Key Words: lymph nodes • Peyer's patches • spleen • p65 • TNFR1


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