Springer Semin Immun (2005) 26:385–404 DOI 10.1007/s00281-004-0185-z ORIGINAL PAPER Christoph J. Binder · Gregg J. Silverman Natural antibodies and the autoimmunity of atherosclerosis Published online: 18 December 2004  Springer-Verlag 2004 Abstract In recent years, the subject of natural antibodies has been revisited and the im- munobiological roles of these humoral factors are being better defined. These antibodies are secreted by distinct sets of innate-like B cells, B-1 cells and marginal zone B cells, which arise early in development to become the sources of “natural immune memory”. Due to their interactions with a variety of self-determinants, natural antibodies have previ- ously been postulated to play roles in the maintenance of host homeostasis. A central para- digm has recently been developed from the demonstration that oxidation derived epitopes on apoptotic cells and oxidized low-density lipoproteins are recognized by the phospho- rylcholine-specific germline encoded B-1 cell natural antibody, T15, which has provided important insights into possible “house-keeping” functions under both normal and patho- logical conditions. In this review, the potential functions of natural antibodies in the pathogenesis and progression of the chronic inflammatory condition of atherosclerosis are discussed, as well as their capacities for apoptotic cell binding and clearance. These inter- actions of natural antibodies and oxidation-epitopes from phospholipids appear to provide a dynamic immunobiological connection linking host responses in infection, autoimmuni- ty and atherosclerosis. Keywords B-1 cell · Tolerance · Repertoire · Apoptosis · Host immunity Introduction Understanding the functional and structural properties of natural antibodies (NAbs) has been a topic of interest for several decades [26], but in recent years there has been a criti- cal re-examination of the roles of these humoral factors in host defenses. In general, NAbs are defined as antibodies that spontaneously arise without prior infection or defined im- mune exposure. At birth, most serum immunoglobulins are of the IgM isotype, and these C. J. Binder · G. J. Silverman ( ) ) Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0663, USA e-mail: gsilverman@ucsd.edu · Tel.: +1-858-5345439 · Fax: +1-858-5345399