An Immunoglobulin Light Chain

Identification of the immunogens responsible for the production of pathogenic autoantibodies is a major problem in the field of autoimmunity. In the principal diseases that are thought to involve autoimmunization, rheumatoid arthritis, type I diabetes, and multiple sclerosis are examples, the instigating stimulus is unknown. Another example of the gap in our knowledge of disease-causing immunogens can be found in SLE. The characteristic autoantibody of lupus binds to double-strand (ds) DNA yet this nucleic acid antigen is barely immunogenic, even in lupus-prone MRL-lpr/lpr mice (1) . Certain bacterial DNAs can elicit anti-dsDNA antibodies in normal mice, but those antibodies and the spontaneously produced anti-DNA antibodies of SLE have different serological specificities (2). By contrast with the poor immunogenicity of mammalian dsDNA, other forms of DNA, such as Z-DNA (a double-strand molecule with a leftward spiraling helix instead of the right-handed helical structure of dsDNA), elicit brisk immune responses in MLR-lpr/lpr mice as well as in normal mice and rabbits (1, 3) . The lack of immunogenicity of exogenous dsDNA does not disprove the participation of endogenous DNA in the origins of anti-DNA antibodies, however. Cell nuclei, for example, might release a form of dsDNA that is peculiarly immunogenic in patients with SLE. In addition to nucleic acids, several polypeptides associated with uridine-rich small nuclear ribonucleoprotein (snRNP) particles are also important autoantigens in SLE. Patients with SLE and associated diseases (mixed connective tissue disease, scleroderma, rheumatoid arthritis, and Sjogren's syndrome) produce two categories of autoantibodies against these particles: anti-RNP antibodies, which bind the Ul snRNPspecific polypeptides 70 kD, A, andC, andanti-Sm antibodies, which bind to a shared epitope in the B', B, and D snRNP polypeptides (4) . Anti-RNP autoantibodies, according to one hypothesis, originate from the release of snRNP antigens from the nuclei ofdead or injured cells (5). The finding that normal mice respond to immuni-