Contribution of the spleen, lymph nodes and bone marrow to the antibody response in collagen-induced arthritis in the rat.

The relative contribution of different lymphoid tissues to the anti-CII antibody response was studied in rats with arthritis produced as a result of immunizing them with collagen type II (CII). Antibody production was measured by maintaining lymphoid cells in short-term culture in collagen-coated microculture wells: the antibody they secreted was determined directly by a modified ELISA. Systemic sensitization to CII was established within a week of immunization, and a stronger response in the local draining lymph nodes relative to the spleen was associated with the development of clinical disease. From experiments involving splenectomy and adoptive cell transfer, the spleen was ascribed a suppressive role in controlling both arthritis and total antibody production. The bone marrow was found to be an important site of antibody production and the greater production of antibody by cells from tibial marrow in limbs with arthritis, compared with healthy limbs, argues for a local immune response to degrading joint antigens that may have systemic suppressive or protective properties. It is concluded that local immunity reflects the state of disease and that the antibodies produced by different lymphoid tissues may be made in response to different stimuli, and that the antibodies in turn may have different pathological effects.