Interaction of the Hinge Region of Human Immunoglobulin G with a Murine Lymphocyte Membrane Receptor. Relevance to the Problem of Antiglobulin Induction in Rheumatoid Arthritis

Evidence is presented which indicates the presence on murine lymphocytes of a membrane receptor for determinants on the hinge region of human IgG. These determinants are exposed following pepsin scission of IgG molecule, i.e. on the F(ab')2 fragment. The evidence for a hinge receptor derives, in vivo, from splenic localization of F(ab')2 in germinal centres and, in vitro, from immunofluorescent binding studies. The sequential immunofluorescent pattern for the uptake of human F(ab)2 fragments into murine spleen germinal centres was identical with that previously observed for heat-aggregated human IgG, but F(ab')2 fragments appeared to be retained in the germinal centres for a shorter time than aggregated IgG. Experiments with nude mice and T cell-deprived mice showed that the localization of F(ab')2 fragments does not require T cells. Competition experiments suggest that the receptor for F(ab')2 may bear little relation to the receptor for aggregated IgG. The relevance of such a lymphocyte membrane receptor to the immunopathology of rheumatoid arthritis is discussed in the light of previous findings that a proportion of the serum IgG of patients with rheumatoid arthritis has a structural anomaly compared with control IgG, characterized exposure of new determinants at the hinge region.