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Lymphocyte Activation and the Family of NF-κB Transcription Factor Complexes

  • Chapter
Mechanisms in B-Cell Neoplasia 1992

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 182))

Abstract

NF-κB is a transcription factor complex known for some time to play a pivotal role in the regulated expression of a large number of genes which are activated during an immune response. Antigen in the context of the appropriate antigen presenting cell (APC) leads to the proliferation of T cells and the expression of factors (predominantly cytokines) from the competent T cells. These factors in turn stimulate various cells involved in an immune response. Both the signal emanating from the initial antigenic encounter and the secondary factor-mediated responses in other cells involve NF-κB, at least in part. For example, NF-κB has been shown to be essential for the regulated expression of the immunoglobulin k light chain (whence the name NF-κB, a nuclear factor binding to the kappa light chain B element), the tumor necrosis factor alpha (TNF-α) and beta (TNF-β), interferon-β, the IL-2 receptor, the IL-6 cytokine, the IL-2 growth factor, GM-CSF, G-CSF, and MHC-Class I, just to name a few immunomodulatory gene products. NF-κB is implicated also in the induction of various acute phase proteins (e.g. angiotensinogen), some transcription factors/oncogenes (e.g. IRF-1 and c-myc) and, most importantly, in the induction of various viruses, including the human immunodeficiency virus (HIV), cytomegalovirus, adenovirus and SV40. NF-κB mediates its effects through so-called κB elements; the consensus sequence for a κB site reads GGGRNNYYCC, but additional variants exist to which NF-κB binds. A variety of agents as well as factors produced by stimulated cells activate NF-κB in the respective target cells; included among these are a large array of T cell mitogens (e.g. lectins, anti CD3 and anti CD2 antibodies, in addition to antigen/APC), the factors TNF-α and TNF-β, IL-1, double-stranded RNA, chemical agents which cause PKC activation, DNA damaging agents and treatments which produce oxygen radicals. In addition, several viruses have been shown to cause NF-κB activation like the HTLV-I and -II viruses, the HSV-1 virus, the HHV-6 virus, the Hepatitis B virus and the adenovirus. These viruses apparently subvert the cellular mechanisms to induce an activation phenotype in cells. The listing given here for agents which activate NF-κB and for genes regulated by NF-κB is only a partial one and is only meant to convey the central role this transcription factor plays during cellular activation and, in particular, during immune activation (for a complete listing and the appropriate References see recent reviews [1, 2]).

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Authors and Affiliations

  1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Md, 20892, USA

    V. Bours, G. Franzoso, K. Brown, S. Park, V. Azarenko, M. Tomita-Yamaguchi & U. Siebenlist

  2. Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Md, 20892, USA

    K. Kelly

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Editors and Affiliations

  1. Laboratory of Genetics, National Cancer Institute National Institutes of Health, Bldg. 37, Rm 2B04, Bethesda, MD, 20892, USA

    Michael Potter M. D (Chief) (Chief)

  2. Institute for Immunology, Grenzacherstr. 487, CH-4005, Basel, Switzerland

    Fritz Melchers (Director) (Director)

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Bours, V. et al. (1992). Lymphocyte Activation and the Family of NF-κB Transcription Factor Complexes. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1992. Current Topics in Microbiology and Immunology, vol 182. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77633-5_52

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  • DOI: https://doi.org/10.1007/978-3-642-77633-5_52

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