Anti-Sm autoantibodies in MRL mice: in vitro detection and generation of antibody-forming cells.

Open Access
Publisher Website
Google Scholar
Abstract
Antibodies to the nuclear antigen SM are specific for systemic lupus erythematosus in humans and mice. In order to study the cellular mechanisms of anti-Sm generation, a hemolytic plaque assay to identify and enumerate lymphocytes secreting anti-Sm has been developed by using SRBC coated with purified Sm by a modified carbodiimide technique. Anti-Sm-specific PFC were found in MRL/Mp-Ipr/Ipr and MLR/Mp- +/+ mice whose sera contained anti-Sm, but were never detected in anti-Sm-negative MRL mice or in normals. Spleen cells from anti-Sm-positive MRL/Mp-Ipr/Ipr mice generated anti-Sm PFC spontaneously after 4 days of in vitro culture, whereas cells from normal mice or anti-Sm-negative MRL mice were never observed to produce spontaneous anti-Sm, even when cultured in the presence of bacterial lipopolysaccharide. The generation of anti-Sm by MRL cells in vitro was found to be dependent on the presence of T cells, but the ability of cells from individual MRL mice to generate anti-Sm appeared to be limited by the availability of Sm-specific B cell precursors and not due to a relative absence of T cells capable of providing help for the anti-Sm response. Analysis at the cellular level of the in vitro generation of a disease-specific autoantibody by using the methods described should facilitate understanding of mechanisms of autoreactivity.