A B S T R A C T The metabolism of radioiodinated IgG was studied in 20 patients with rheumatoid arthritis and 11 normal controls using autologous IgG and homologous IgG pooled from normal donors. Fractional catabolic rates in the controls were 4.44% of the autologous-and 4.29% of the homologouslabeled protein per day. The corresponding rates in the rheumatoid patients were 9.67% of the autologousand 8.64% of the homologous-labeled protein per day. Extravascular catabolism occurred only in the rheumatoid group and accounted essentially for the entire increased catabolism ofIgG observed in these patients. 10 patients were especially hypercatabolic, with fractional catabolic rates for autologous IgG greater than 10%. Moreover, they catabolized their autologous IgG significantly faster than the homologous IgG (12.6 vs. 9.9%). The increment of catabolism of autologous over homologous IgG also occurred in the extravascular compartment. These highly hypercatabolic patients had a significantly increased number of manifestations of extra-articular disease.The hypercatabolism of IgG could not be correlated with age, weight, sex, duration of disease, joint erosions, corticosteroid therapy, erythrocyte sedimentation rate, rheumatoid factor titer, serum IgG concentration, or circulating immune complexes as measured by the Raji cell radioimmunoassay.Conceivable sites of extravascular catabolism and possible causes of faster catabolism of autologous (rheumatoid) than of homologous (normal) IgG are discussed.

The pathogenetic anti-erythrocyte autoantibody responses of NZB mice were characterized at the level of the autoantibody secreting B lymphocyte. Clonal heterogeneity was evaluated by reference to certain phenotypic expressions of immunoglobulin heavy chain constant and variable region genes. The anti-X autoantibody response appeared completely restricted to the NZB strain and was predominantly of IgG class. Specific anti-X B2 lymphocytes exhibited marked clonal diversity in regard to immunoglobulin class and heterogeneity of autoantibody affinity as determined by competitive plaque inhibition assays. The anti-HB autoantibody response, a genetically non-restricted response, was predominantly of IgM class; splenic anti-HB B2 lymphocytes also exhibited marked clonal diversity in respect to immunoglobulin class and binding affinity of the secreted autoantibody. Neither response exhibited a maturational increase in homogeneity similar to that observed in anti-sheep red cell responses by NZB mice. These data indicate that heterogeneous sets of B lymphocytes are recruited in these responses, an observation consistent with the concept that the immunogenesis of these pathogenetic autoimmune responses may be immunoregulatory in nature.