类风湿性关节炎（RA）是一类主要累及滑膜及其周围组织的多系统炎性自身免疫性疾病。虽然CD1dhiCD5+B细胞亚群对EAE和SLE的抑制已被证实，但其对RA炎症反应的作用，对RA的免疫调节，以及在RA中，该群B细胞的自身成熟、分化和其表达IL-10的免疫调控机制尚未阐述。前期工作中，利用II型胶原在IL-10敲除的小鼠模型上成功诱导RA的发生，却未能在同种野生型小鼠模型上诱导成功，验证了IL-10抑制RA的发生。本课题将：1）明确表达IL-10的CD1dhiCD5+ B细胞对RA发生发展的作用；2）阐明此亚群B细胞对RA炎症的免疫调节；3）明确II型胶原致敏对CD1dhiCD5+B细胞的增殖、分化和IL-10在该亚群细胞表达的调节是否抗原特异；4）探讨在胶原诱导RA发生的情况下，调节CD1dhiCD5+ B细胞的信号传导途径。此课题完成后，将有可能为临床RA的细胞免疫抑制治疗提供实验依据。

Rheumatoid arthritis (RA) is a class of inflammatory autoimmune disease, which involve multi-systems of body, especially in synovium and its surrounding tissues. Although, the inhibition of EAE and SLE development by CD1dhiCD5+ B cell subset have been demonstrated. However, the functions of this regulatory B cell subset has not been described in RA, especially for CD1dhiCD5 + B cells how to regulate the inflammation and immune reaction of RA. Also, the immune regulatory mechanism for CD1dhiCD5+ B subset maturation, differentiation, and expression of IL-10 in this B cell subset has not yet been elaborated in RA disease..In our previous work, type II collagen has been used to induce RA successfully in IL-10 knockout mouse model, but could not be induced in wild-type mouses. These results validated that IL-10 can delay RA initiation and inhibit RA development. This project will be on the basis of previous research to conduct: 1) study the effect of IL-10 expression CD1dhiCD5+ B cells on RA initiation and development; 2) clarify the immune regulatory mechanism of this subgroup of B cells in RA inflammation; 3) clarify whether type II collagen can induce CD1dhiCD5+ B cell subset proliferation, differentiation and regulate IL-10 expression in this B cell subset are antigen specificity; 4) explore the signal transduction pathway for regulating CD1dhiCD5+ B-cell proliferation, differentiation and IL-10 expression in this B cell subset in collagen inducing RA. After completion of this project, it will be possible to provide experimental evidence for clinical RA cell immunosuppressive therapy.