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Suppression of IL-4- and CD40-induced B-lymphocyte activation by intravenous immunoglobulin is not mediated through the inhibitory IgG receptor FcγRIIb

2002; Elsevier BV; Volume: 110; Issue: 3 Linguagem: Inglês

10.1067/mai.2002.127284

1097-6825

Qianli Zhuang, Sandra Bisotto, Elizabeth D. Fixman, Bruce Mazer,

Platelet Disorders and Treatments

Abstract Background : Intravenous immunoglobulin (IVIG) has been used extensively in the treatment of autoimmune and allergic diseases, but the precise mechanism behind its efficacy remains unclear. Ligation of the low-affinity IgG Fc receptor FcγRIIb can inhibit B-lymphocyte activation. Our laboratory has shown that IVIG suppresses proliferation and IgE production by human B cells stimulated with IL-4 and anti-CD40 antibodies. Objective : We sought to determine whether the regulatory action of IVIG is mediated through binding FcγRIIb, phosphorylation of the receptor, and induction of phosphatases, including SH2-containing inositol-5′-phosphatase. Methods : All experiments were performed on human tonsillar B cells. Phenotyping was performed by means of flow cytometry. Cells were cultured with IL-4 and anti-CD40 antibodies with or without IVIG (10 mg/mL), and FCγRIIb receptor activation and phosphorylation were measured by means of Western blot analysis. Results : FcγRIIb was the predominant isoform of Fcγ receptor expressed on tonsillar B cells, and preincubation with IVIG failed to block binding of FcγRIIb antibody. Anti-FcγRIIb antibodies did not reverse inhibition of B-cell proliferation or IgE production by IVIG. Treatment of stimulated B lymphocytes with IVIG for 1 to 60 minutes did not change the global protein tyrosine phosphorylation pattern, except for tyrosine phosphorylation of an unidentified 30-kd protein. We directly examined tyrosine phosphorylation of FcγRIIb and its downstream-associated phosphatase, SH2-containing inositol-5′-phosphatase. Both remained unchanged after IVIG treatment, as did other related phosphatases. Conclusion : These data argue against the involvement of FcγRIIb in the inhibition of CD40/IL-4-induced B-cell activation by IVIG. (J Allergy Clin Immunol 2002;110:480-3.)