Rheumatoid factor synthesis will be studied in pokeweed mitogen-stimulated populations of blood mononuclear cells from patients with rheumatoid arthritis and control individuals. The modulation of this response by helper and suppressor T cells will be examined. The effect of gold salt and D-penicillamine therapy on the morphological and functional characteristics of peripheral blood monocytes and lymphocytes in patients with rheumatoid arthritis will be studied. A factor secreted by macrophages that facilitates differentiation of B cells into immunoglobulin-secreting cells will be characterized. The T and B cell populations involved in responsiveness to staphylococcal protein A will also be characterized. Immunoregulatory derangements in patients with autoimmune disease will be further studied. Studies will be conducted to obtain a better understanding of LE skin disease in order to gain insight into mechanisms of injury which may apply to certain extracutaneous sites. The studies are designed to investigate the humoral and cellular aspects of autoimmunity to DNA in relationship to immunoglobulin accumulation at the dermal-epidermal junction on the one hand, and in inflammatory skin lesions on the other. Studies of the role of binding and phagocytosis of immune complexes in the margination and sequestration of the neutrophil will be conducted. The potential role of macrophages in the generation of a tolerance defect in New Zealand mice will be examined. Ontogeny of a B cell tolerance defect in New Zealand mice will also be examined. The role of a variety of antigens in this tolerance defect will be examined. Finally, the mechanism of tolerance induction by high and low epitope density forms of TNP-HGG will be further investigated.
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