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During the progression of atherosclerosis, autoantibodies are induced to epitopes of oxidized low-density lipoprotein (oxLDL) and active immunization of hypercholesterolemic mice with oxLDL ameliorates atherogenesis. We unexpectedly found that many autoantibodies to oxLDL derived from 'naive' atherosclerotic mice share complete genetic and structural identity with antibodies from the classic anti-phosphorylcholine B-cell clone, T15, which protect against common infectious pathogens, including pneumococci. To investigate whether in vivo exposure to pneumococci can affect atherogenesis, we immunized Ldlr(-/-) mice with Streptococcus pneumoniae. This induced high circulating levels of oxLDL-specific IgM and a persistent expansion of oxLDL-specific T15 IgM-secreting B cells primarily in the spleen, which were cross-reactive with pneumococcal determinants. Pneumococcal immunization decreased the extent of atherosclerosis, and plasma from these mice had an enhanced capacity to block the binding of oxLDL to macrophages. These studies show molecular mimicry between epitopes of oxLDL and S. pneumoniae and indicate that these immune responses can have beneficial effects.

Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). In this study, we evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPLs were preferentially bound by Lp[a] [a] and cysteine 4326 of apolipoprotein B-100 (apoB-100) form a disulfide bond to create an Lp[a] particle (2-6). The clinical interest in Lp[a] emanates from its association with cardiovascular disease (CVD) when present in high plasma concentrations. A meta-analysis of prospective studies demonstrated that elevated levels of Lp[a] are an independent risk factor for CVD (7). The pro-atherogenic influence of Lp[a] seems to be particularly enhanced in subjects with elevated levels of LDL cholesterol (8, 9).The gene for apo [a] appeared recently on the evolutionary scale and is present only in humans and nonhuman primates. An unrelated apo[a]-like gene consisting only of KIII repeats is also present in hedgehogs and is postulated to have evolved independently through divergent evolution (10). The physiological role of Lp[a] and the underlying mechanisms through which it contributes to CVD are unknown. One hypothesis suggests that Lp[a] promotes thrombosis by inhibiting thrombolysis. Apo [a] has

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