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.