Takai T, Ono M, Hikida M, Ohmori H, Ravetch J V
Department of Biotechnology, Faculty of Engineering, Okayama University, Japan.
Nature. 1996 Jan 25;379(6563):346-9. doi: 10.1038/379346a0.
Despite its widespread distribution on both lymphoid and myeloid cells, the biological role of the low-affinity immunoglobulin-G receptor, Fc gamma RII, is not fully understood. Defects in this receptor or its signalling pathway in B cells result in perturbations in immune-complex-mediated feedback inhibition of antibody production. We now report that Fc gamma RII-deficient animals display elevated immunoglobulin levels in response to both thymus-dependent and thymus-independent antigens. Additionally, the effector arm of the allergic response is perturbed in these mice. Mast cells from Fc gamma RII-/- are highly sensitive to IgG-triggered degranulation, in contrast to their wild-type counterparts. Fc gamma RII-deficient mice demonstrate an enhanced passive cutaneous analphylaxis reaction, the result of a decreased threshold for mast-cell activation by Fc gamma RIII cross-linking. These results demonstrate that Fc gamma RII acts as a general negative regulator of immune-complex-triggered activation in vivo for both the afferent and efferent limbs of the immune response. Exploiting this property offers new therapeutic opportunities for the treatment of allergic and autoimmune disorders.
尽管低亲和力免疫球蛋白G受体FcγRII在淋巴细胞和髓细胞上广泛分布，但其生物学作用尚未完全明确。B细胞中该受体或其信号通路的缺陷会导致免疫复合物介导的抗体产生反馈抑制出现紊乱。我们现在报告，FcγRII缺陷型动物对胸腺依赖性和胸腺非依赖性抗原的反应中免疫球蛋白水平升高。此外，这些小鼠的过敏反应效应臂也受到干扰。与野生型肥大细胞相比，FcγRII-/-小鼠的肥大细胞对IgG触发的脱颗粒高度敏感。FcγRII缺陷型小鼠表现出增强的被动皮肤过敏反应，这是FcγRIII交联激活肥大细胞阈值降低的结果。这些结果表明，FcγRII在体内作为免疫复合物触发的免疫反应激活的一般负调节因子，作用于免疫反应的传入和传出分支。利用这一特性为治疗过敏性和自身免疫性疾病提供了新的治疗机会。
