Targeted disruption of the Rel/NF-kappaB family members NF-kappaB2, encoding 
p100/p52, and RelB in mice results in anatomical defects of secondary lymphoid 
tissues. Here, we report that development of Peyer's patch (PP)-organizing 
centers is impaired in both NF-kappaB2- and RelB-deficient animals. IL-7-induced 
expression of lymphotoxin (LT) in intestinal cells, a crucial step in PP 
development, is not impaired in RelB-deficient embryos. LTbeta receptor 
(LTbetaR)-deficient mice also lack PPs, and we demonstrate that LTbetaR 
signaling induces p52-RelB and classical p50-RelA heterodimers, while tumor 
necrosis factor (TNF) activates only RelA. LTbetaR-induced binding of p52-RelB 
requires the degradation of the inhibitory p52 precursor, p100, which is 
mediated by the NF-kappaB-inducing kinase (NIK) and the IkappaB kinase (IKK) 
complex subunit IKKalpha, but not IKKbeta or IKKgamma. Activation of RelA 
requires all three IKK subunits, but is independent of NIK. Finally, we show 
that TNF increases p100 levels, resulting in the specific inhibition of RelB DNA 
binding via the C-terminus of p100. Our data indicate an important role of 
p52-RelB heterodimers in lymphoid organ development downstream of LTbetaR, NIK 
and IKKalpha.