Yoshizaki Ayumi
Department of Dermatology, The University of Tokyo Graduate School of Medicine.
Nihon Rinsho Meneki Gakkai Kaishi. 2016;39(3):197-206. doi: 10.2177/jsci.39.197.
One of the major roles of B cells is to generate antibodies to specific antigens. Secreted antibodies are the principal molecules involved in humoral immunity, with the capacity not only to neutralize pathogens, but also to enhance their elimination by activating phagocytosis or complement proteins. Recently, it has been highlighted that B cells exert important regulatory roles independent of their antibody producing function. These roles include efficiently presenting antigens to the T cells, secreting cytokines, and inducing immune cell differentiation. Thus, B cells have emerged as cells that play crucial roles in immune systems in addition to producing antibodies. Systemic sclerosis (SSc) is characterized by autoimmunity and tissue fibrosis of several organs. Although the pathogenic relationship between systemic autoimmunity and the clinical manifestations of SSc remains unknown, SSc patients display a variety of abnormal immune activation including the production of disease-specific autoantibodies. Previous studies have demonstrated that immune cells, mainly including B cells, play a critical role in systemic autoimmunity and disease expression, though the role of autoimmunity in generating the clinical and pathologic phenotype in SSc remains uncertain. SSc patients have B cell abnormalities characterized by chronic hyper-reactivity of memory B cells. Although distinct subsets of autoantibodies do not have a proven pathogenic role, they are selectively associated with unique disease manifestations. To date, the treatment of SSc has largely relied on cytotoxic immunosuppressants and corticosteroids. Although this has resulted in improved disease survival, these patients may still suffer severe adverse events and refractory disease to conventional immunosuppressive therapies. Recently, clinical trials involving the chimeric monoclonal antibody rituximab have raised high expectations. B cell depleting therapy with rituximab offers a promising treatment for the rheumatic autoimmune diseases including SSc. This article reviews the current knowledge of B cell biology and pathogenesis in SSc as well as the therapeutic approaches focusing on the targeting of B cell specific surface molecules and on the blocking of B cell activation and survival.
B细胞的主要作用之一是产生针对特定抗原的抗体。分泌的抗体是体液免疫中的主要分子，不仅能够中和病原体，还能通过激活吞噬作用或补体蛋白来促进病原体的清除。最近，有研究强调B细胞发挥着独立于其抗体产生功能的重要调节作用。这些作用包括有效地将抗原呈递给T细胞、分泌细胞因子以及诱导免疫细胞分化。因此，B细胞除了产生抗体外，还成为在免疫系统中发挥关键作用的细胞。系统性硬化症（SSc）的特征是自身免疫和多个器官的组织纤维化。尽管系统性自身免疫与SSc临床表现之间的致病关系尚不清楚，但SSc患者表现出多种异常的免疫激活，包括产生疾病特异性自身抗体。先前的研究表明，免疫细胞（主要包括B细胞）在系统性自身免疫和疾病表达中起关键作用，尽管自身免疫在SSc临床和病理表型形成中的作用仍不确定。SSc患者存在B细胞异常，其特征为记忆B细胞的慢性高反应性。尽管不同亚群的自身抗体尚未被证实具有致病作用，但它们与独特的疾病表现存在选择性关联。迄今为止，SSc的治疗主要依赖于细胞毒性免疫抑制剂和皮质类固醇。尽管这已提高了疾病生存率，但这些患者仍可能遭受严重的不良事件以及对传统免疫抑制疗法难治的疾病。最近，涉及嵌合单克隆抗体利妥昔单抗的临床试验带来了很高的期望。用利妥昔单抗进行B细胞清除疗法为包括SSc在内的风湿性自身免疫疾病提供了一种有前景的治疗方法。本文综述了目前关于SSc中B细胞生物学和发病机制的知识，以及针对B细胞特异性表面分子靶向、阻断B细胞激活和存活的治疗方法。
