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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2961-2967.
Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-08-041772.
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Submitted August 15, 2006
Accepted November 12, 2006
TACI regulates IgA production by APRIL in collaboration with HSPG
Daisuke Sakurai, Hidenori Hase, Yumiko Kanno, Hidefumi Kojima, Ko Okumura, and Tetsuji Kobata*
Dokkyo Medical University School of Medicine, Japan
Juntendo University, Japan
* Corresponding author; email: tkobata{at}dokkyomed.ac.jp.
Transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) is a member of the tumor necrosis factor (TNF) receptor family that serves as a receptor for both B cell activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL). Although TACI is reported to function as a positive or negative regulator for B cell responses, its roles remain elusive. Experiments using TACI siRNA into B cells indicated that TACI positively regulated APRIL-induced IgA production in collaboration with heparan sulfate proteoglycans (HSPG). Furthermore, TACI negatively regulated BAFF-induced B-cell proliferation and production of IgA and IgG. In addition, B cells treated with heparitinase to denature HSPG showed that HSPG is essential for APRIL-induced B-cell responses such as B-cell proliferation, IgG and IgA production, and induction of activation-induced cytidine deaminase (AID) and non-canonical NF- B2. In contrast, phosphorylation of physiological AID kinase, protein kinase A (PKA), was dependent on TACI. Importantly, co-ligation of TACI and HSPG by specific antibodies, but not TACI or HSPG ligation itself, could induce the phosphorylation of PKA and IgA production instead of APRIL. Our findings indicate that simultaneous binding of TACI and HSPG on B cells with APRIL is crucial for IgA production.
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