炎症细胞被募集到眼眶并分泌细胞因子导致纤维化的机制是IgG4相关性眼眶病（IgG4-ROD）发生、发展的关键。前期研究发现B淋巴细胞在IgG4-ROD的发生发展中起重要作用：CD20在IgG4-ROD患者病变组织中阳性表达率达100%，而外周血表达正常；抗CD20单抗局部注射能控制IgG4-ROD，降低患者的炎症纤维化程度。但存在部分患者不能完全控制，需多次给药，甚至无效的问题。同时，研究发现负向免疫调节因子——调节性B细胞（Breg）在IgG4相关性疾病（IgG4-RD）患者中比例较正常人低；抗CD20治疗Breg浓度急剧降低；长期临床缓解者Breg比例较治疗前提高。上述研究基础提示Breg通过抗CD20介导的信号通路调控IgG4-ROD 纤维化的可能存在。本课题拟明确：Breg在抗CD20调控IgG4相关性眼眶病纤维化中的机制。本研究将为IgG4-ROD的防治提供新的思路和治疗靶点。

The collection to the orbit and the secretion of the cyctokine of the inflammatory cells induce inflammatory fibrosis are the major causes of the IgG4-related orbital disease (IgG4-ROD). Our previous studies shown that B lymphocyte is important in the development of IgG4-ROD: CD20 is 100% expressed in the tissues of IgG4-ROD, whlie normal in peripheral blood; intraorbital injection of anti-CD20 antibody is effective in IgG4-ROD, can induced reduction in inflammatory fibroblasts. But there are some patients still cannot be controled, need multiple dosing, and even donot response to the drug. In the mean while, negative immune adjustment factor——regulatory B cell (Breg) is expressed lower in IgG4-related disease (IgG4-RD) patients than normal person; Breg can be led to remission during anti-CD20 antibody treatment; and long-term clinical remission is associated with a higher ratio of Breg than before treatment. All above indicate that Breg may enhance anti-CD20 antibody therapy to affect the secretion of inflammatory cells and cytokines that induce fibrosis. Our research intends to clarify the machanism of the effect and regulation of fibrosis by Breg during anti-CD20 antibody immunotherapy in IgG4-ROD. Our reaseach will provide new ideas and therapeutic targets to the prevention and treatment of IgG4-ROD.