Hiepe F, Alexander T, Voll R E
Medizinische Klinik m. S. Rheumatologie und Klinische Immunologie, Deutsches RheumaForschungszentrum Berlin - ein Institut der Leibniz-Gemeinschaft, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland,
Z Rheumatol. 2015 Feb;74(1):20-5. doi: 10.1007/s00393-014-1438-4.
Plasma cells are specialized terminally differentiated B cells that synthesize and secrete antibodies to maintain humoral immunity. By the production of pathogenic antibodies, plasma cells contribute to the development of many conditions, such as autoimmune disorders, transplant rejection and allergies. Two different plasma cell compartments can independently generate different types of pathogenic antibodies: (1) short-lived plasmablasts (proliferating precursors of mature plasma cells) and plasma cells, which live only as long as B cells are activated. Consequently, these cells cause disease flares that respond to immunosuppressive drugs and B cell targeting therapies. (2) Long-lived non-proliferating memory plasma cells, which survive in niches in bone marrow and inflamed tissues for months, years or a lifetime independent of B or T cell help or antigen contact. Because they do not respond to immunosuppressants or treatment targeting B cells, they are responsible for refractory chronic conditions. Therefore, long-lived memory plasma cells in particular have emerged as important therapeutic targets and strategies to target these cells are discussed in this article. So far long-lived plasma cells can only be depleted by immunoablative therapy with antithymocyte globulin in the setting of stem cell transplantation or by treatment with proteasome inhibitors approved for multiple myeloma. These strategies provide options for treating refractory autoantibody-mediated diseases. One interesting approach aims at an antigen-specific elimination of target plasma cells without depleting the protective plasma cells responsible for maintaining humoral immunity.
浆细胞是特化的终末分化B细胞,可合成并分泌抗体以维持体液免疫。通过产生致病性抗体,浆细胞促成了许多病症的发展,如自身免疫性疾病、移植排斥反应和过敏反应。两种不同的浆细胞区室可独立产生不同类型的致病性抗体:(1)短命的浆母细胞(成熟浆细胞的增殖前体)和浆细胞,其寿命仅与B细胞被激活的时间一样长。因此,这些细胞会引发对免疫抑制药物和B细胞靶向疗法有反应的疾病发作。(2)长寿的非增殖性记忆浆细胞,它们在骨髓和炎症组织的特定微环境中存活数月、数年或终生,独立于B细胞或T细胞的辅助或抗原接触。由于它们对免疫抑制剂或靶向B细胞的治疗无反应,所以它们是难治性慢性病的病因。因此,长寿记忆浆细胞尤其已成为重要的治疗靶点,本文将讨论针对这些细胞的策略。到目前为止,长寿浆细胞只能在干细胞移植的情况下通过用抗胸腺细胞球蛋白进行免疫清除疗法或用批准用于多发性骨髓瘤的蛋白酶体抑制剂进行治疗来清除。这些策略为治疗难治性自身抗体介导的疾病提供了选择。一种有趣的方法旨在特异性清除靶浆细胞而不消耗负责维持体液免疫的保护性浆细胞。