TACI attenuates antibody production costimulated by BAFF-R and CD40.
B cell activating factor of the TNF family (BAFF), plays critical roles in B cell survival, activation, differentiation, and antibody (Ab) production. BAFF binds to three receptors: BAFF-R, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen. While BAFF-R is the primary receptor for B cell costimulation by BAFF, TACI is reported to serve as a positive or negative regulator for B cell responses depending on conditions. To determine the real role of TACI in B cell responses, we examined the functional relationship between TACI and BAFF-R in Ab production from human peripheral blood B cells using agonistic mAb. BAFF-R and CD40 enhanced IgG secretion and B cell proliferation, which were inhibited by TACI. Although TACI induced mild B cell apoptosis, its extent did not correlate with that of TACI-mediated inhibition of IgG secretion. In addition, TACI inhibited B-lymphocyte-induced maturation protein-1 expression, IgG secretion from previously IgG-negative selected B cells, and activation-induced cytidine deaminase expression enhanced by BAFF-R and CD40. Importantly, BAFF-R and CD40 enhanced B cell responsiveness to TACI-mediated suppression. Thus, BAFF may attenuate T cell-independent and -dependent B cell responses by TACI.
Sakurai
Daisuke
D
Department of Immunology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
Kanno
Yumiko
Y
Hase
Hidenori
H
Kojima
Hidefumi
H
Okumura
Ko
K
Kobata
Tetsuji
T
D000276:Adjuvants, Immunologic / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000502:physiology; D000917:Antibody Formation; D017209:Apoptosis / Q000276:immunology; D053265:B-Cell Activation Factor Receptor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000502:physiology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D015398:Signal Transduction / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D053265:B-Cell Activation Factor Receptor; D019013:CD40 Antigens; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein