B-cell selection and the development of autoantibodies.
B-cell selection and the development of autoantibodies.
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B 细胞选择和自身抗体的开发。
DOI：
10.1186/ar3918
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发表时间：
2012
影响因子：
4.9
通讯作者：
Clark EA
中科院分区：
文献类型：
--
作者：
Giltiay NV;Chappell CP;Clark EA
B细胞在人体自身免疫中发挥重要作用的最明确证据是，消耗B细胞的免疫疗法对许多自身免疫性疾病都是非常有效的治疗方法。所有人，无论健康与否，都有自身反应性B细胞，但频率不同。许多基因影响这些自身反应性B细胞的水平，以及它们在骨髓（BM）的中心检查点或外周淋巴组织的检查点发育过程中是否被消除。这些基因包括编码通过B细胞受体复合物（如Btk和PTPN22）调节信号传导的蛋白质，通过toll样受体（TLRs）（如MyD88和白细胞介素-1受体相关激酶4）调节先天信号传导的蛋白质，以及编码激活诱导脱氨酶（AID）的基因，该基因对B细胞进行类别转换重组和体细胞超突变至关重要。最近的研究表明，TLR信号元件和AID不仅在外周B细胞中起作用，帮助介导对外来抗原的有效抗体反应，而且在B细胞发育的早期阶段，在BM中帮助清除自身反应性B系细胞。新生成的B细胞离开基底膜进入血液和脾红髓后，可同时表达AID和TLR信号元件如TLR7，完全具备对抗原（包括自身抗原）的快速反应、同型类转换和体细胞超突变的能力。因此，这些红髓B细胞可能是产生自身抗体的细胞的重要来源，特别是在滤泡外部位，实际上可能与生发中心产生的B细胞一样是产生自身抗体的重要来源。
The clearest evidence that B cells play an important role in human autoimmunity is that immunotherapies that deplete B cells are very effective treatments for many autoimmune diseases. All people, healthy or ill, have autoreactive B cells, but not at the same frequency. A number of genes influence the level of these autoreactive B cells and whether they are eliminated or not during development at a central checkpoint in the bone marrow (BM) or at a later checkpoint in peripheral lymphoid tissues. These genes include those encoding proteins that regulate signaling through the B-cell receptor complex such as Btk and PTPN22, proteins that regulate innate signaling via Toll-like receptors (TLRs) such as MyD88 and interleukin-1 receptor-associated kinase 4, as well as the gene encoding the activation-induced deaminase (AID) essential for B cells to undergo class switch recombination and somatic hypermutation. Recent studies have revealed that TLR signaling elements and AID function not only in peripheral B cells to help mediate effective antibody responses to foreign antigens, but also in the BM to help remove autoreactive B-lineage cells at a very early point in B-cell development. Newly arising B cells that leave the BM and enter the blood and splenic red pulp can express both AID and TLR signaling elements like TLR7, and thus are fully equipped to respond rapidly to antigens (including autoantigens), to isotype class switch, and to undergo somatic hypermutation. These red pulp B cells may thus be an important source of autoantibody-producing cells arising particularly in extrafollicular sites, and indeed may be as significant a source of autoantibody-producing cells as B cells arising from germinal centers.
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影响因子：
3.6
作者：
Dil, Nyla;Marshall, Aaron J.
通讯作者：
Marshall, Aaron J.
影响因子：
158.5
作者：
Arbuckle, MR;McClain, MT;Harley, JB
通讯作者：
Harley, JB
Toll样受体9控制鼠狼疮中的抗DNA自身抗体产生。
DOI：
10.1084/jem.20050338
发表时间：
2005-07-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Christensen SR;Kashgarian M;Alexopoulou L;Flavell RA;Akira S;Shlomchik MJ
通讯作者：
Shlomchik MJ
DOI：
10.4049/jimmunol.1000983
发表时间：
2010-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Colonna L;Catalano G;Chew C;D'Agati V;Thomas JW;Wong FS;Schmitz J;Masuda ES;Reizis B;Tarakhovsky A;Clynes R
通讯作者：
Clynes R
DOI：
10.4049/jimmunol.0713370
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Arechiga AF;Habib T;He Y;Zhang X;Zhang ZY;Funk A;Buckner JH
通讯作者：
Buckner JH