NF-kappaB pathways in the immune system: control of the germinal center reaction.
The NF-kappaB signaling pathway plays a critical role in regulating innate and adaptive immunity. This is clearly evident as mouse models deficient for numerous NF-kappaB subunits and upstream activators exhibit defects in the immune system ranging from impaired development of lymphocytes to defective adaptive immune responses. In this review, we focus on the role that NF-kappaB plays in the germinal center (GC) reaction. Specifically, we discuss the major NF-kappaB subunits and the IkappaB homolog, Bcl-3. Recent findings reveal that Bcl-6, an unrelated transcriptional repressor, is functionally similar to Bcl-3 as both factors may suppress p53 activity to allow for efficient GC formation to occur. We discuss potential mechanisms of action for Bcl-3 and Bcl-6 in this highly complex, but important process of B-cell affinity maturation.
Goetz
Christine A
CA
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, 405 West Dr., Room 213, Chapel Hill, NC 27599, USA. cgoetz@med.unc.edu
Baldwin
Albert S
AS
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D018858:Germinal Center / Q000276:immunology / Q000502:physiology; D007107:Immune System / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000276:immunology* / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000276:immunology* / Q000378:metabolism
D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53