Clonal evolution and antigen recognition of anti-nuclear antibodies in acute systemic lupus erythematosus.
Clonal evolution and antigen recognition of anti-nuclear antibodies in acute systemic lupus erythematosus.
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DOI：
10.1038/s41598-017-16681-y
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发表时间：
2017-11-27
影响因子：
4.6
通讯作者：
Kikutani H
中科院分区：
文献类型：
--
作者：
Sakakibara S;Arimori T;Yamashita K;Jinzai H;Motooka D;Nakamura S;Li S;Takeda K;Katayama J;El Hussien MA;Narazaki M;Tanaka T;Standley DM;Takagi J;Kikutani H
系统性红斑狼疮（SLE）中疾病相关自身抗体的演变过程仍有待确定。在这里，我们展示了SLE中产生抗核抗体（ANA）的B细胞的克隆内多样化和亲和力成熟。我们确定了一组单克隆ANA识别核抗原，如双链DNA（dsDNA）和核糖核蛋白（RNP）从急性SLE受试者。这些ANA相对较少，但仍然是关键的突变。血液淋巴细胞的高通量免疫球蛋白测序揭示了存在相当大的ANA谱系在克隆内剪切关键突变。我们进一步关注抗DNA抗体，其能够以高亲和力结合单链（ss）和dsDNA。晶体结构和生化分析证实了突变在获得DNA反应性中的直接作用，并且还揭示了这些抗DNA抗体识别DNA双链体内的未配对区域。我们的研究揭示了高亲和力抗DNA抗体的独特性质，这些抗体是在SLE急性期通过抗原驱动的亲和力成熟产生的。
The evolutional process of disease-associated autoantibodies in systemic lupus erythematosus (SLE) remains to be established. Here we show intraclonal diversification and affinity maturation of anti-nuclear antibody (ANA)-producing B cells in SLE. We identified a panel of monoclonal ANAs recognizing nuclear antigens, such as double-stranded DNA (dsDNA) and ribonucleoproteins (RNPs) from acute SLE subjects. These ANAs had relatively few, but nonetheless critical mutations. High-throughput immunoglobulin sequencing of blood lymphocytes disclosed the existence of sizable ANA lineages shearing critical mutations intraclonally. We further focused on anti-DNA antibodies, which are capable to bind to both single-stranded (ss) and dsDNA at high affinity. Crystal structure and biochemical analysis confirmed a direct role of the mutations in the acquisition of DNA reactivity and also revealed that these anti-DNA antibodies recognized an unpaired region within DNA duplex. Our study unveils the unique properties of high-affinity anti-DNA antibodies that are generated through antigen-driven affinity maturation in acute phase of SLE.
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影响因子：
3.6
作者：
Kalsi, JK;Martin, ACR;Isenberg, DA
通讯作者：
Isenberg, DA
影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
14.9
作者：
Li S;Yamashita K;Amada KM;Standley DM
通讯作者：
Standley DM
影响因子：
17.1
作者：
Andrews SF;Huang Y;Kaur K;Popova LI;Ho IY;Pauli NT;Henry Dunand CJ;Taylor WM;Lim S;Huang M;Qu X;Lee JH;Salgado-Ferrer M;Krammer F;Palese P;Wrammert J;Ahmed R;Wilson PC
通讯作者：
Wilson PC
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