Fletcher Carrie A, Sutherland Andrew P R, Groom Joanna R, Batten Marcel L, Ng Lai Guan, Gommerman Jennifer, Mackay Fabienne
Immunology and Inflammation Research Program, The Garvan Institute of Medical Research, Sydney, Australia.
Eur J Immunol. 2006 Sep;36(9):2504-14. doi: 10.1002/eji.200636270.
B cell-activating factor belonging to the TNF family (BAFF) is a B cell survival factor required for B cell maturation. BAFF transgenic (Tg) mice develop autoimmune disorders characterized by autoantibody production, which leads to nephritis and salivary gland destruction (sialadenitis), features reminiscent of systemic lupus erythematosus and Sjögren's syndrome (SS), respectively. Disease in BAFF Tg mice correlates with the expansion of the marginal zone (MZ) B cell compartment and the abnormal presence of MZ-like B cells in the blood, LN and inflamed salivary glands, suggesting a role for these cells in BAFF-induced autoimmunity. Lymphotoxin-beta (LTbeta)-deficient mice show disrupted splenic architecture, lack MZ B cells and some peripheral LN, and are unable to mount T cell-dependent immune responses. BAFF Tg mice lacking LTbeta (LTbetaDelta-BTg) retained these defects, yet still developed nephritis associated with the presence of B-1 B cells in the kidneys. However, in contrast to old BAFF Tg mice, aging LTbetaDelta-BTg mice no longer developed sialadenitis. Thus, autoimmune disorders in BAFF Tg mice are possibly events coordinated by MZ and B-1 B cells at separate anatomical sites.
肿瘤坏死因子家族的B细胞激活因子（BAFF）是B细胞成熟所需的B细胞存活因子。BAFF转基因（Tg）小鼠会出现以自身抗体产生为特征的自身免疫性疾病，这分别导致肾炎和唾液腺破坏（涎腺炎），这些特征分别让人联想到系统性红斑狼疮和干燥综合征（SS）。BAFF Tg小鼠的疾病与边缘区（MZ）B细胞区室的扩张以及血液、淋巴结和炎症唾液腺中出现异常的MZ样B细胞有关，这表明这些细胞在BAFF诱导的自身免疫中发挥作用。淋巴毒素-β（LTβ）缺陷小鼠表现出脾脏结构破坏，缺乏MZ B细胞和一些外周淋巴结，并且无法产生T细胞依赖性免疫反应。缺乏LTβ的BAFF Tg小鼠（LTβΔ - BTg）保留了这些缺陷，但仍会发展出与肾脏中B - 1 B细胞存在相关的肾炎。然而，与年老的BAFF Tg小鼠不同，衰老的LTβΔ - BTg小鼠不再发生涎腺炎。因此，BAFF Tg小鼠中的自身免疫性疾病可能是由MZ和B - 1 B细胞在不同解剖部位协调发生的事件。
