Role of toll-like receptors in primary Sjogren's syndrome with a special emphasis on B-cell maturation within exocrine tissues
Role of toll-like receptors in primary Sjogren's syndrome with a special emphasis on B-cell maturation within exocrine tissues
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DOI：
10.1016/j.jaut.2012.01.016
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发表时间：
2012-08-01
影响因子：
12.8
通讯作者：
Youinou, Pierre
中科院分区：
文献类型：
--
作者：
Guerrier, Thomas;Le Pottier, Laetitia;Youinou, Pierre
无论是生发中心（GC）还是边缘区（MZ）的滤泡细胞，所有幼稚成熟的B淋巴细胞都需要紧张性信号来维持生命。我们推断原发性干燥综合征患者唾液腺中增殖的B淋巴细胞也是如此。根据B细胞浸润，选择11个SG和3个扁桃体样本进行进一步检查。使用CD20与CD10、CD21、CD27、CD38或IgD的组合对组织切片进行染色。它们也被激光显微切割用于转录因子的定量RT-PCR。GC特异性激活诱导的胞苷脱氨酶（AID）和TLR9。一些B细胞聚集体被证明是真正的GC根据其膜标记，而其他的过渡II型B细胞的集群。这些包含Notch-2和Blimp-1的mRNA，但不包含Pax-5、Bcl-6和AID的mRNA。出乎意料的是，在这些MZ B细胞簇中发现了TLR 9的mRNA，但在真实的GC中没有。TLR9不仅传递足够的紧张信号以保持B细胞存活，而且它们还赋予自身反应性B细胞MZ样表型。因此。TLR可能是未来生物治疗的目标。(C)2012爱思唯尔有限公司保留所有权利。
Be they follicular cells within the germinal centers (GCs) or marginal zone (MZ), all naive mature B lymphocytes need tonic signaling to stay alive. We reasoned that the same holds true for those B lymphocytes that proliferate in the salivary glands (SGs) of patients with primary Sjogren's syndrome. Based on B cell infiltration, 11 SGs and three tonsil samples were selected for further examination. Tissue sections were stained using CD20 combined with CD10, CD21, CD27, CD38 or IgD. They were also laser-microdissected for quantitative RT-PCR of transcription factors. GC-specific activation-induced cytidine deaminase (AID) and TLR9. Some B cell aggregates proved to be real GCs according to their membrane markers, whereas others were clusters of transitional type II B cells. These contained mRNAs for Notch-2 and Blimp-1, but not for Pax-5, Bcl-6 and AID. Unanticipated was the finding of mRNAs for TLR9 in these clusters of MZ B-cells, but not in the real GCs. Not only do TLR9 deliver sufficiency of tonic signaling to keep B cells alive, but they also confer autoreactive B cells with an MZ-like phenotype. Thus. TLRs might be targets for forthcoming biotherapies. (C) 2012 Elsevier Ltd. All rights reserved.