BAFF, APRIL and their receptors: structure, function and signaling.
BAFF, APRIL and their receptors play important immunological roles, especially in the B cell arm of the immune system. A number of splice isoforms have been described for both ligands and receptors in this subfamily, some of which are conserved between mouse and human, while others are species-specific. Structural and mutational analyses have revealed key determinants of receptor-ligand specificity. BAFF-R has a strong selectivity for BAFF; BCMA has a higher affinity for APRIL than for BAFF, while TACI binds both ligands equally well. The molecular signaling events downstream of BAFF-R, BCMA and TACI are still incompletely characterized. Survival appears to be mediated by upregulation of Bcl-2 family members through NF-kappaB activation, degradation of the pro-apototic Bim protein, and control of subcellular localization of PCKdelta. Very little is known about other signaling events associated with receptor engagement by BAFF and APRIL that lead for example to B cell activation or to CD40L-independent Ig switch.
Bossen
Claudia
C
Biochemistry Department, University of Lausanne, Boveresses 155, CH-1066 Epalinges, Switzerland.
Schneider
Pascal
P
D017398:Alternative Splicing; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D053264:B-Cell Activating Factor / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053265:B-Cell Activation Factor Receptor / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053301:B-Cell Maturation Antigen / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000502:physiology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D016328:NF-kappa B / Q000502:physiology; D052002:NF-kappa B p50 Subunit / Q000502:physiology; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D053303:Transmembrane Activator and CAML Interactor Protein / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; C486361:Tnfrsf13b protein, mouse; C486662:Tnfrsf13c protein, mouse; C491959:Tnfsf13 protein, mouse; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D051745:Protein Kinase C-delta