Mice with a targeted disruption of the Rel/nuclear factor-kappa B fami
ly member RelB develop a complex inflammatory phenotype, myeloid hyper
plasia, and splenomegaly due to extramedullary hemopoiesis. In this wo
rk, we report that RelB-deficient mice, in addition to the pathologic
changes, were highly susceptible to infection by the facultative intra
cellular bacterium Listeria monocytogenes, RelB binds transcriptionall
y active kappa B motifs in the TNF-alpha promoter in normal cells, and
in vitro studies with macrophages isolated from RelB-deficient animal
s revealed impaired production of TNF-alpha in response to LPS and IFN
-gamma. RelB-deficient mice also were unable to mount a protective imm
une response against lymphocytic choriomeningitis virus. These results
indicate a defective T cell-macrophage interaction and cytotoxic T ce
ll response, respectively, in mice lacking RelB. Analysis of resting a
nd specific Ab production demonstrated that while RelB is not required
for the secretion of Ig isotypes that result from heavy chain class s
witching, it is necessary for normal production of Ag-specific IgC in
response to T cell-dependent and -independent stimuli. Thus, RelB is n
ot only essential for a normal hemopoietic system in the unchallenged
animal, but also involved in various specific and nonspecific immune r
esponses.