TACItly changing tunes: farewell to a yin and yang of BAFF receptor and TACI in humoral immunity? New genetic defects in common variable immunodeficiency.
OBJECTIVE
The complex system of the tumour necrosis factor ligands BAFF and APRIL and their three receptors BCMA, TACI and BAFF receptor and its role in B-cell development and function is the objective of extensive research. Whereas the importance of BAFF/BAFF receptor interactions for B-cell survival could be clearly demonstrated, TACI is believed to counteract BAFF activity as a negative regulator in the murine model. The primarily immunodeficient phenotype of human TACI deficiency, however, claims a distinct function of this receptor in human peripheral B-cell development, class switch recombination and terminal differentiation.


RESULTS
Common variable immunodeficiency comprises a heterogeneous group of antibody deficiency syndromes characterized by impaired terminal B-cell differentiation. By means of molecular genetics common variable immunodeficiency is still ill-defined, but the description of the deficiency of the inducible costimulator in a small subgroup of common variable immunodeficiency patients set the starting point for the molecular dissection of this disease entity. The recent discovery of genetic defects in the tumour necrosis factor receptor superfamily members TACI and BAFF receptor in patients with common variable immunodeficiency denotes further advances in this field.


CONCLUSIONS
In this review we will discuss recent progress made in the understanding of the BAFF/APRIL-TACI/BCMA/BAFF receptor system in relation to the recent discovery that mutations in human TACI cause a primary humoral immunodeficiency. This suggests a refined role for TACI in human B-cell biology.
Salzer
Ulrich
U
Department of Clinical Immunology and Rheumatology, Medical Center, University of Freiburg, Freiburg, Germany.
Grimbacher
Bodo
B
D000818:Animals; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D001402:B-Lymphocytes / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D006801:Humans; D038041:Lymphopoiesis; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; C114631:TNFSF13 protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha