title: Transmembrane activator and calcium-modulator and cyclophilin ligand interactor mutations in common variable immunodeficiency.
abstract: OBJECTIVE
  TNFRSF13B, the gene which encodes transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is mutated in nearly 10% of patients with common variable immune deficiency (CVID), an antibody deficiency syndrome characterized by loss of memory B cells and plasma cells. This review discusses the normal function of TACI and the role of TACI mutants in CVID.
  
  
  RESULTS
  TACI activates isotype switching, mediates immunoglobulin production in response to type II T-independent antigens, and plays an inhibitory role in B cell homeostasis. Recent evidence indicates that TACI synergizes with CD40 and Toll-like receptors for immunoglobulin secretion and promotion of plasma cell differentiation. The two most common TACI mutants associated with CVID--C104R and A181E--are primarily found as heterozygous mutations suggesting that they either cause haploinsufficiency or exert a dominant negative effect. TACI mutations in CVID are associated with an increased susceptibility to autoimmunity and lymphoproliferation.
  
  
  CONCLUSIONS
  TACI has a dual function in promoting B cell antibody responses and inhibiting B cell proliferation. The observation that TACI mutations are present in healthy participants suggests that modifier genes may play an important role in the development of CVID. The discovery of these genes will help understand the pathogenesis of this disease.
authors.affiliation: Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Esra
authors.initials: E
authors.lastname: Ozcan
authors.forename: Ingrid
authors.initials: I
authors.lastname: Rauter
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D051379:Mice; D009154:Mutation; D011485:Protein Binding / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D053303:Transmembrane Activator and CAML Interactor Protein / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; C108467:TNFRSF13B protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13