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Roles of the NF-κB Pathway in B-Lymphocyte Biology

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B Cell Receptor Signaling

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 393))

Abstract

NF-κB was originally identified as a family of transcription factors that bind the enhancer of the immunoglobulin κ light-chain gene. Although its function in the regulation of immunoglobulin κ light-chain gene remains unclear, NF-κB plays critical roles in development, survival, and activation of B lymphocytes. In B cells, many receptors, including B-cell antigen receptor (BCR), activate NF-κB pathway, and the molecular mechanism of receptor-mediated activation of IκB kinase (IKK) complex has been partially revealed. In addition to normal B lymphocytes, NF-κB is also involved in the growth of some types of B-cell lymphomas, and many oncogenic mutations involved in constitutive activation of the NF-κB pathway were recently identified in such cancers. In this review, we first summarize the function of NF-κB in B-cell development and activation, and then describe recent progress in understanding the molecular mechanism of receptor-mediated activation of the IKK complex, focusing on the roles of the ubiquitin system. In the last section, we describe oncogenic mutations that induce NF-κB activation in B-cell lymphoma.

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Abbreviations

CBM:

CARMA1–BCL10–MALT1

CSR:

Class-switch recombination

CYLD:

Cylindromatosis

DAG:

Diacylglycerol

DUB:

Deubiquitinating enzyme

GC:

Germinal center

IκB:

Inhibitor of nuclear factor-κB

ITAM:

Immunoreceptor tyrosine-based activation motifs

IKK:

IκB kinase

LUBAC:

Linear ubiquitin chain assembly complex

NEMO:

NF-κB essential modifier

NF-κB:

Nuclear factor-κB

NIK:

NF-κB-inducing kinase

OTU:

Ovarian tumor domain

OTULIN:

OTU DUB with linear linkage specificity

PKC:

Protein kinase C

TD:

Thymus-dependent

TI:

Thymus-independent

TLR:

Toll-like receptor

TRAF:

TNF receptor-associated factor

UBAN:

Ubiquitin binding in ABIN proteins and NEMO

WT:

Wild type

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  1. Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan

    Yoshiteru Sasaki & Kazuhiro Iwai

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  1. WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan

    Tomohiro Kurosaki

  2. Cellular and Molecular Immunology, Georg August University Goettingen, Göttingen, Germany

    Jürgen Wienands

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Sasaki, Y., Iwai, K. (2015). Roles of the NF-κB Pathway in B-Lymphocyte Biology. In: Kurosaki, T., Wienands, J. (eds) B Cell Receptor Signaling. Current Topics in Microbiology and Immunology, vol 393. Springer, Cham. https://doi.org/10.1007/82_2015_479

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