title: Unexpected functions of nuclear factor-κB during germinal center B-cell development: implications for lymphomagenesis.
abstract: OBJECTIVE
  B-cell tumors originating from the transformation of germinal center B cells frequently harbor genetic mutations, leading to constitutive activation of the nuclear factor-κB (NF-κB) signaling pathway. The present review highlights recent insights into the roles of separate NF-κB transcription factors in germinal center B-cell development and discusses implications of the results for germinal center lymphomagenesis.
  
  
  RESULTS
  Understanding how aberrant NF-κB activation promotes tumorigenesis requires the understanding of the role of NF-κB in the tumor-precursor cells. Despite extensive knowledge on NF-κB biology, the function of this complex signaling pathway in the differentiation of germinal center B cells is largely unknown. The present review will discuss recent findings that revealed distinct roles of separate NF-κB transcription factors during the germinal center reaction in the context of germinal center lymphomagenesis. Most notably, a single NF-κB subunit, c-REL, was found to be required for the maintenance of the germinal center reaction and was associated with the activation of a metabolic program that promotes cell growth.
  
  
  CONCLUSIONS
  Identifying the biological roles of the separate NF-κB transcription factor subunits in germinal center biology will help to better understand the pathogenic consequences of their constitutive activation in B-cell tumors. This knowledge may be exploited for the development of targeted antitumor therapies aimed at inhibiting selectively those components of aberrant NF-κB activity which contribute to pathogenesis.
authors.affiliation: aDepartment of Pathology & Cell Biology bDepartment of Microbiology & Immunology cHerbert Irving Comprehensive Cancer Center, Columbia University, New York, New York, USA.
authors.forename: Ulf
authors.initials: U
authors.lastname: Klein
authors.forename: Nicole
authors.initials: N
authors.lastname: Heise
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D021122:Protein Subunits