Unexpected functions of nuclear factor-kappa B during germinal center B-cell development: implications for lymphomagenesis

作者：Klein Ulf^*; Heise Nicole

来源：Current Opinion in Hematology, 2015, 22(4): 379-387.

DOI：10.1097/MOH.0000000000000160

• B-cell lymphoma
• germinal center
• lymphomagenesis
• nuclear factor-kappa B

Purpose of review
B-cell tumors originating from the transformation of germinal center B cells frequently harbor genetic mutations, leading to constitutive activation of the nuclear factor-kappa B (NF-kappa B) signaling pathway. The present review highlights recent insights into the roles of separate NF-kappa B transcription factors in germinal center B-cell development and discusses implications of the results for germinal center lymphomagenesis.
Recent findings
Understanding how aberrant NF-kappa B activation promotes tumorigenesis requires the understanding of the role of NF-kappa B in the tumor-precursor cells. Despite extensive knowledge on NF-kappa B 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-kappa B transcription factors during the germinal center reaction in the context of germinal center lymphomagenesis. Most notably, a single NF-kappa B 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.
Summary
Identifying the biological roles of the separate NF-kappa B 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-kappa B activity which contribute to pathogenesis.

• 出版日期2015-7