Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren's syndrome
Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren's syndrome
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DOI：
10.1172/jci200214121
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发表时间：
2002-01-01
影响因子：
15.9
通讯作者：
Mackay, F
中科院分区：
文献类型：
--
作者：
Groom, J;Kalled, SL;Mackay, F
BAFF（BLyS，TALL-1，THANK，zTNF 4）是特异性调节B淋巴细胞增殖和存活的TNF超家族成员。BAFF转基因小鼠（Tg）会发生类似于系统性红斑狼疮的自身免疫性疾病。我们现在证明，BAFF Tg小鼠，随着年龄的增长，发展的继发性病理学让人想起干燥综合征（SS），这是表现为严重的涎腺炎，唾液分泌减少，并破坏颌下腺。在人类中，SS还与循环BAFF水平升高以及发炎唾液腺中BAFF表达的显著上调相关。BAFF Tg小鼠中疾病的可能解释是对自身反应性B细胞的过度存活信号，可能是因为它们在脾脏中成熟时通过关键的耐受检查点。边缘区（MZ）B细胞室是BAFF Tg小鼠脾脏中扩大的B细胞亚群之一，是自身反应性B细胞的潜在储存库。有趣的是，具有MZ样表型的B细胞浸润BAFF Tg小鼠的唾液腺，表明该隔室的细胞可能参与SS和可能的其他自身免疫性疾病的组织损伤。我们的结论是，改变B细胞分化和过多的BAFF诱导的耐受性可能是SS发病机制的核心。
BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate that BAFF Tg mice, as they age, develop a secondary pathology reminiscent of Sjogren's syndrome (SS), which is manifested by severe sialadenitis, decreased saliva production, and destruction of submaxillary glands. In humans, SS also correlates with elevated levels of circulating BAFF, as well as a dramatic upregulation of BAFF expression in inflamed salivary glands. A likely explanation for disease in BAFF Tg mice is excessive survival signals to autoreactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. The marginal zone (MZ) B cell compartment, one of the enlarged B cell subsets in the spleen of BAFF Tg mice, is a potential reservoir of autoreactive B cells. Interestingly, B cells with an MZ-like phenotype infiltrate the salivary glands of BAFF Tg mice, suggesting that cells of this compartment potentially participate in tissue damage in SS and possibly other autoimmune diseases. We conclude that altered B cell differentiation and tolerance induced by excess BAFF may be central to SS pathogenesis.