Anti-DNA Abs are the most frequently encountered self-reactivity, a curious fact that may be explained by their potential for cross-reactivity and multireactivity. A case in point is 3H9, an anti-DNA, anti-chromatin Ab, isolated from a diseased MRL/lpr mouse (1). 3H9 cross-reacts with anionic phospholipids, including phosphatidylserine, an Ag exposed on apoptotic cells (2). 3H9 is also multireactive: it binds DNA as well as purified nucleosomes (3). The binding of 3H9 to DNA can be measured by a variety of techniques, but EMSAs demonstrate most clearly that 3H9 forms a specific complex with DNA and that it greatly prefers poly (dG)· poly (dC) over poly (dA)· poly (dT)(4).

Multireactivity of anti-DNAs has been the focus of several studies including a recent study in this journal by Guth et al.(5). Multireactivity of 3H9 derives from its asymmetric combining site: the DNA-binding surface is located in the H chain and can be enlarged by adding arginine residues to certain sites in V H complementarity-determining regions and FR3 (1). This leaves the L chain free to recognize additional determinants of a complex Ag. Strikingly, different immunofluorescence patterns are seen when the 3H9 H chain is paired with different L chains, although most pairs bind DNA (1). Therefore, 3H9, like other Abs to DNA, has a complex specificity that, depending on the L chain, can extend to other nucleic acids, such as RNA, and include protein-DNA complexes, such as nucleosomes (1).