Abstract
It has been more than a decade since it was recognized that the nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) transcription factor family was activated by two distinct pathways: the canonical pathway involving NF-κB1 and the non-canonical pathway involving NF-κB2. During this time a great deal of evidence has been amassed on the ligands and receptors that activate these pathways, the cytoplasmic adapter molecules involved in transducing the signals from receptors to nucleus, and the resulting physiological outcomes within body tissues. In contrast to NF-κB1 signaling, which can be activated by a wide variety of receptors, the NF-κB2 pathway is typically only activated by a subset of receptor and ligand pairs belonging to the tumor necrosis factor (TNF) family. Amongst these is B cell activating factor of the TNF family (BAFF) and its receptor BAFFR. Whilst BAFF is produced by many cell types throughout the body, BAFFR expression appears to be restricted to the hematopoietic lineage and B cells in particular. For this reason, the main physiological outcomes of BAFF mediated NF-κB2 activation are confined to B cells. Indeed BAFF mediated NF-κB2 signaling contributes to peripheral B cell survival and maturation as well as playing a role in antibody responses and long term maintenance plasma cells. Thus the importance BAFF and NF-κB2 permeates the entire B cell lifespan and impacts on this important component of the immune system in a variety of ways.
Highlights
In 2001 it was recognized that nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling consisted of two distinct pathways which have become known as the canonical and non-canonical pathways [1]
This review focuses on NF-κB2 activation by BAFFR and its ligand BAFF and the specific outcomes for tissues which express this receptor
The authors did suggest that the defect they observed in BAFFR-deficient mice was less severe than that observed in BAFF-deficient mice. If this is the case it does suggest that BCMA or TACI, while not playing any essential role in germinal center (GC) maintenance as indicated by the phenotypes of their respective knockout mice, may be able to compensate for some of the functions of BAFFR in its absence. It is highly likely given the involvement of BAFFR and its strong activation of the NF-κB2 pathway, that NF-κB2 signaling is involved in GC maintenance
Summary
In 2001 it was recognized that nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) signaling consisted of two distinct pathways which have become known as the canonical (classical/NF-κB1) and non-canonical (alternative/NF-κB2) pathways [1]. Processing of NF-κB2 to its active form, p52 only occurs upon signal-induced activation of the pathway [3] and it is the loss of the carboxyterminus of p100, which facilitates translocation of active p52/RelB dimers to the nucleus. In both pathways the presence of NF-κB dimers in the nucleus initiates specific transcription programs via the binding of dimers to κB sequences in the promoters of various genes. Given the almost complete confinement of BAFFR expression to B cells, the effects of BAFF/BAFFR induced NF-κB2 on B cell survival, maturation, and responses will be described
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