Burioni Roberto, Canducci Filippo, Saita Diego, Perotti Mario, Mancini Nicasio, De Marco Donata, Clementi Nicola, Chieffo Alaide, Denaro Maurizio, Cianflone Domenico, Manfredi Angelo A, Colombo Antonio, Maseri Attilio, Clementi Massimo
Università Vita-Salute San Raffaele, Milano, Italy.
J Immunol. 2009 Aug 15;183(4):2537-44. doi: 10.4049/jimmunol.0901076. Epub 2009 Jul 27.
Recent data indicated that adaptive immunity is involved in the process of atherogenesis. Oligoclonal recruitment of T lymphocytes has been described in coronary plaques of patients with acute coronary syndrome. However, the nature of immune response remains to be determined. In the present study, we examined the Ab response in six coronary plaques obtained by endoluminal directional atherectomy. The IgG1/kappa-coding gene repertoires of B lymphocytes present in circulating blood and in coronary plaques were cloned and analyzed. In all of the six plaques, we observed 1) a skewed usage of heavy and light IgG1/kappa Ab-coding genes, 2) an oligoclonal distribution of V(K), J(K), and V(H), D(H), and J(H) genes with overrepresentation of some rarely used IgG genes, and 3) the unequivocal signs of Ag-driven clonal expansion and evolution of B cells. The data document for the first time the presence of a local Ag-driven clonal evolution of B cells in human atherosclerotic plaques.
近期数据表明，适应性免疫参与动脉粥样硬化的形成过程。在急性冠状动脉综合征患者的冠状动脉斑块中已发现T淋巴细胞的寡克隆募集。然而，免疫反应的本质仍有待确定。在本研究中，我们检测了通过腔内定向斑块旋切术获取的六个冠状动脉斑块中的抗体反应。对循环血液和冠状动脉斑块中存在的B淋巴细胞的IgG1/κ编码基因库进行了克隆和分析。在所有六个斑块中，我们观察到：1）重链和轻链IgG1/κ抗体编码基因的使用偏向；2）V(K)、J(K)以及V(H)、D(H)和J(H)基因的寡克隆分布，一些很少使用的IgG基因过度表达；3）明确的抗原驱动的B细胞克隆扩增和进化迹象。这些数据首次证明了人类动脉粥样硬化斑块中存在局部抗原驱动的B细胞克隆进化。
