Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease.
Members of the tumor necrosis factor receptor superfamily (TNFRSF) participate prominently in B-cell maturation and function. In particular, B-cell activating factor belonging to the TNF family receptor (BAFF-R), B-cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) play critical roles in promoting B-cell survival at distinct stages of development by engaging a proliferation-inducing ligand (APRIL) and/or BAFF. CD40 is also essential for directing the humoral response to T-cell-dependent antigens. Signaling by the TNFRSF is mediated primarily, albeit not exclusively, via the TNFR-associated factor (TRAF) proteins and activation of the canonical and/or non-canonical nuclear factor-κB (NF-κB) pathways. Dysregulated signaling by TNFRSF members can promote B-cell survival and proliferation, causing autoimmunity and neoplasia. In this review, we present a current understanding of the functions of and distinctions between APRIL/BAFF signaling by their respective receptors expressed on particular B-cell subsets. These findings are compared and contrasted with CD40 signaling, which employs similar signaling conduits to achieve distinct cellular outcomes in the context of the germinal center response. We also underscore how new findings and conceptual insights into TNFRSF signaling are facilitating the understanding of B-cell malignancies and autoimmune diseases.
Program on Inflammatory Disease Research, Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA. robert@sanfordburnham.org
Robert C
RC
Rickert
Julia
J
Jellusova
Ana V
AV
Miletic
D000818:Animals; D001327:Autoimmune Diseases; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D019013:CD40 Antigens; D016328:NF-kappa B; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13