Roles of the NF- B Pathway in Lymphocyte Development and Function

Abstract

This article focuses on the functions of NF-kB that vitally impact lymphocytes and thus adaptive immunity.NF-kB has long been known to be essential for many of the responses of mature lymphocytes to invading pathogens.In addition, NF-kB has important functions in shaping the immune system so it is able to generate adaptive responses to pathogens.In both contexts, NF-kB executes critical cell-autonomous functions within lymphocytes as well as within supportive cells, such as antigen-presenting cells or epithelial cells.It is these aspects of NF-kB's physiologic impact that we address in this article. CELL-AUTONOMOUS ROLES OF NF-kB IN LYMPHOCYTE DEVELOPMENTNF-kB makes numerous cell-autonomous contributions to the development of mature T and B lymphocytes.Given the importance of NF-kB in adaptive immune responses mediated by mature lymphocytes, it seems prudent for developing lymphocytes to have adopted a strategy in which their maturation hinges on a properly functioning NF-kB system.As discussed later, the primary, though not exclusive, contribution of NF-kB to lymphocyte development is to assure cell survival.These antiapoptotic functions of NF-kB remain crucial for the health of lymphocytes even after they mature.Unfortunately, these functions also aid tumorigenesis when NF-kB is dysregulated (Vallabhapurapu and Karin 2009).Most of the insights about the role of NF-kB in development of lymphocytes have come from analyses of genetically manipulated mice in which NF-kB components are missing or in which NF-kB activation has been compromised or is constitutively induced.B and T lymphocytes will be discussed in parallel to highlight similarities at related stages of their development.Figures 1 and 2 summarize some of the findings described later. Early Lymphocyte ProgenitorsDespite a clear role for the NF-kB homolog Dorsal in early Drosophila development (Hong et al. 2008), in mammalian development no such role for NF-kB has emerged, including development of early lymphocyte precursors.NF-kB can, however, play a protective role in precursors to