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* Università Vita-Salute San Raffaele and
Istituto Scientifico San Raffaele, Milano, Italy,
Bracco Imaging, San Donato Milanese, Italy; and
Heart Care Foundation, Firenze, Italy
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/
-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/
Ab-coding genes, 2) an oligoclonal distribution of VK, JK, and VH, DH, and JH 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was partially supported by the Italian Ministry of University and Research (PRIN) and by an institutional research grant form Bracco Imaging.
M.C., R.B., F.C., and A.M. designed the study, analyzed data, and wrote the paper; F.C. and D.S. performed experiments, analyzed data, and wrote the paper; D.D.M. performed experiments; M.P., N.M., and N.C. analyzed data; A.A.M., M.D., and D.C. commented on the manuscript; and A.C. and A.C. performed endarterectomies and enrolled patients. All authors declare that they participated in the study and that they have seen and approved the final version.
2 R.B. and F.C. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Massimo Clementi, Università Vita-Salute San Raffaele, Via Olgettina 60, 20132 Milano, Italy. E-mail address: massimo.clementi{at}hsr.it
4 Abbreviations used in this paper: ACS, acute coronary syndrome; CPS, coronary plaque sample; EDA, endoluminal directional artherectomy; HC, H chain; LC, L chain; PBL, peripheral blood lymphocyte.
5 The online version of this article contains supplemental material.
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