TABLE 1.

Major phenotypes associated with deletion of NF-κB family membersa

PhenotypeDescription
NF-κB1−/−Defects in production of Ab and T-cell proliferative responses. Absence of marginal zone B cells. Defect in Th2 responses. Increased susceptibility to S. pneumoniae and L. monocytogenes. Normal response to E. coli infection and H. influenzae but enhanced resistance to EMCV.
NF-κB2−/−Disorganized B- and T-cell areas in spleen and lymph nodes associated with absence of marginal zone macrophages and follicular DC. Reduced numbers of B cells and decreased production of antigen-specific Ab. Increased susceptibility to T. gondii, L. monocytogenes, and L. major but normal response to LCMV.
NF-κB1−/− NFκB2−/−Increased mortality after birth and developmental defects including osteopetrosis, thymic and lymph node atrophy, and disorganized splenic structure.
Re1A−/−Embryonic lethality at day 15 to 16 of gestation due to widespread apoptosis of liver parenchymal cells mediated by TNF. Required for formation of secondary lymphoid organs.
RelB−/−Development of lethal T-cell-mediated inflammatory disease. Impaired production of antigen-specific Ab associated with defects in germinal center formation. Lack of marginal zone B cells and thymic and CD8α DC. Susceptible to L. monocytogenes, LCMV, and T. gondii. Reduced capacity to produce IFN-γ and impaired DTH responses.
c-Rel−/−Impaired T- and B-cell proliferation and reduced Ab responses. Increased susceptibility to L. major and T. gondii. Memory response to influenza virus is impaired. Decreased production of IL-2, IL-3, IL-12, IFN-γ, and GM-CSF.
IκBα−/−Postnatal lethality 7 to 10 days after birth associated with widespread psoriasis-like dermatitis, increased granulopoiesis, and histological alterations in liver and spleen.
Bcl-3−/−Disorganized B- and T-cell areas in spleen. Impaired formation of germinal centers and production of antigen-specific Ab. Defective antigen-dependent priming of T cells. Increased susceptibility to L. monocytogenes, S. pneumoniae, and T. gondii but normal response to E. coli infection.
  • a Abbreviations: Ab, antibody CTL, cytotoxic T lymphocytes; DTH, delayed-type hypersensitivity; DC, dendritic cells; Th1, T helper cells type 1. Adapted from reference 8 with permission of the publisher.