TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts.
The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R-dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons.
Bossen
Claudia
C
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Cachero
Teresa G
TG
Tardivel
Aubry
A
Ingold
Karine
K
Willen
Laure
L
Dobles
Max
M
Scott
Martin L
ML
Maquelin
Aris
A
Belnoue
Elodie
E
Siegrist
Claire-Anne
CA
Chevrier
Stéphane
S
Acha-Orbea
Hans
H
Leung
Helen
H
Mackay
Fabienne
F
Tschopp
Jürg
J
Schneider
Pascal
P
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D053264:B-Cell Activating Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000906:Antibodies; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D008024:Ligands; C505719:TNFSF13B protein, human; C486361:Tnfrsf13b protein, mouse; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13