Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity

IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis

“…IgM and IgG autoantibodies to OxLDL develop in humans and in animal models of atherosclerosis, and their titers often correlate with the extent of disease (5). We have extensively characterized IgM monoclonal anti-OxLDL autoantibodies that were derived from the spleens of atherosclerotic ApoE-deficient mice, as these autoantibodies partially reflect the disease-associated immune responses (6)(7)(8)(9). In vitro, most of these IgMs bound to OxLDL, which is made by copper-catalyzed oxidation of LDL and therefore contains many different oxidation products, including oxidized phospholipids, such as POVPC.…”

“…In vitro, most of these IgMs bound to OxLDL, which is made by copper-catalyzed oxidation of LDL and therefore contains many different oxidation products, including oxidized phospholipids, such as POVPC. Genetic analysis indicated that EO6, the prototypic IgM anti-OxLDL antibody, was a natural antibody secreted by innate B-1 cells in a T cell-independent (TI) manner and possessed the germline-encoded T15 clonotype (8). T15 antibodies have previously been shown to recognize the PC moiety (10), which is an immunodominant component of the cell wall of many microbes, such as Streptococcus pneumoniae (11).…”

Characterization of human monoclonal autoantibody Fab fragments against oxidized LDL

“…However, inconsistent findings that support an anti-atherogenic role have recently challenged this concept. For instance, monoclonal autoantibodies isolated from apoE-deficient mice bind to epitopes of oxLDL and inhibit uptake by macrophages, indicative of a protective role against atherogenesis (Hörkkö et al, 1999;Shaw et al, 2000). Moreover, immunization of rabbits with oxLDL or induction of an immune reaction against oxLDL in mice has a protective effect against atherogenesis (Palinski et al, 1995;Zhou et al, 2001;Binder et al, 2003).…”

“…Moreover, immunization of rabbits with oxLDL or induction of an immune reaction against oxLDL in mice has a protective effect against atherogenesis (Palinski et al, 1995;Zhou et al, 2001;Binder et al, 2003). Limited genetic structures of anti-oxLDL monoclonal antibodies have been analyzed in humans and mice (Shaw et al, 2000(Shaw et al, , 2001Palinski et al, 1996;Choi et al, 1998). Somatic hypermutations have been identified in V H and V L of human antibodies (Shaw et al, 2001).…”

“…Somatic hypermutations have been identified in V H and V L of human antibodies (Shaw et al, 2001). Mouse antibodies are identical in structure to natural T15 anti-phosphorylcholine antibodies that protect against bacterial infection (Shaw et al, 2000).…”