Objective. To investigate the possible association of the Fc␥ receptor IIb (Fc␥RIIb) Ile/Thr187 transmembrane domain polymorphism, which significantly affects receptor signaling, with susceptibility to systemic lupus erythematosus (SLE) in Taiwanese patients.Methods. We used matrix-assisted laser desorption ionization؊time-of-flight mass spectrometry to genotype 351 Taiwanese SLE patients and 372 age-and sex-matched healthy individuals from the same geographic area. Allele frequencies and genotype distributions were compared between the patients and controls, both as an aggregate and as stratified by sex, autoantibody profile, and clinical parameters. A combined analysis was conducted to assess the FCGR2B Thr187 allele as a common risk factor in different ethnic populations.Results. The minor Thr187 allele was significantly associated with SLE in Taiwanese Fc␥RIIb exhibits several apparent inhibitory activities in modulating the immune system, but not all the inhibitory activities are dependent on its distinct ITIM. Coengagement of Fc␥RIIb and other receptors containing an immunoreceptor tyrosine-based activation motif (ITAM) leads to tyrosine phosphorylation of the ITIM by Lyn kinase, recruitment of SH2 domain-containing inositol phosphatase (SHIP), inhibition of ITAMtriggered calcium mobilization, and arrest of cellular proliferation (3). Inhibition of calcium mobilization requires the phosphatase activity of SHIP to hydrolyze phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ), and the

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