Analysis of heavy and light chain use of lupus-associated anti-La/SS-B and anti-Sm autoantibodies reveals two distinct underlying immunoregulatory mechanisms

Abstract

The immunoregulatory mechanisms involved in autoimmune diseases are still unclear. One approach to elucidating these mechanisms involves evaluation of the clonality of the lymphocytes involved in autoimmunity. Molecular analysis of the rearrangement patterns of antigen receptor genes in T cells and B cells has produced ambiguous results. The present study focuses on the analysis of the autoantibodies themselves, being the end products of autoimmune reactivity. Heavy and light chain use of autoantibodies and of total IgG was determined in sera containing anti-La/SS-B and/or anti-Sm antibodies, two autoantibody specificities associated with rheumatic diseases such as systemic lupus erythematosus and Sjögren's syndrome. From our experiments, the anti-La/SS-B response emerges as an oligoclonal, IgG1-restricted B-cell response associated with sharply elevated levels of total serum IgG1-kappa. These characteristics are in sharp contrast to the polyclonal, IgG-subclass-unrestricted anti-Sm response which is accompanied by normal or slightly elevated total serum IgG levels. These findings suggest that anti-La/SS-B autoantibodies, in contrast to anti-Sm autoantibodies, are the product of a restricted oligoclonal B-cell response and thus may be the consequence of a (virally triggered) benign B-cell lymphoma.