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Immunoglobulin and Specific Antibody Synthesis in a Chronic Inflammatory Focus: Antigen-Induced Synovitis¹

From the Department of Internal Medicine, Rheumatic Diseases Unit, University of Texas Southwestern Medical School, Dallas, Texas, and the Veterans Administration Hospital, Dallas, Texas

Abstract

Incorporation of ¹⁴C amino acids into immunoglobulin and specific antibody (anti-BSA) was measured simultaneously in synovial membrane, buffy coat cells and spleen cells of rabbits, utilizing a coprecipitation technique. When immunoglobulin synthesis was measured in the synovial membranes of normal rabbits, small but significant amounts of newly-synthesized immunoglobulin were detected. In one of these animals undergoing a secondary response to BSA, 39.3% of the radioactive globulin synthesized by the synovium was accounted for as anti-BSA. At the same time, 28.4% and 67.2% of the immunoglobulin synthesized by the buffy coat and spleen-cells was also anti-BSA. It was concluded that antibody-forming cells of the recirculating lymphocyte pool enter normal tissue.

A synovial inflammatory reaction was produced by three intra-articular injections of BSA. This was dependent on the appearance of systemic immunity to BSA since no synovitis developed in immunologically tolerant animals. When immunoglobulin and anti-BSA synthesis was measured in two rabbits with synovitis induced by such intra-articular injections, the fraction of globulin synthesized in synovium in the form of specific antibody was found to be 18.2% and 42.2%, respectively, while the fraction found for the spleen cells of the same animals was similar, i.e., 23.7% and 43.7%, respectively. This similarity in specific antibody synthesis in synovium and spleen indicated that the antibody-forming cell populations in both sites were similar.

The synovial membranes of two rabbits given three intra-articular injections of PHA or SLS synthesized large amounts of globulin. This correlated well with the histologic appearance of the tissues, which were infiltrated with lymphocytes and plasma cells. When the amount of anti-BSA synthesized during a secondary response was measured in the synovial membranes, large amounts of radioactivity were accounted for as anti-BSA. The elevated level of synthesis of anti-BSA appeared to be a consequence of the accumulation of specifically committed cells in nonspecifically induced synovial inflammatory foci.

These observations indicate (1) that immunoglobulin and specific antibody-synthesizing cells accumulate in chronic inflammatory foci produced by local injection of antigen or nonspecific inflammatory agents and (2) that the specificity of such antibody-producing cells reflects the overall immune status of the host.

Footnotes

This investigation was supported in part by United States Public Health Service Research Grant AM-09989.

² Clinical Investigator, Veterans Administration Hospital, Dallas, Texas.

³ Recipient, Research Career Award, National Institutes of Health.