Unique site of IgG2a and rheumatoid factor production in MRL/lpr mice

Summary: MRL/lpr (Fas‐deficient) mice develop an autoimmune syndrome associated with excessive production of autoantibodies. A significant portion of these autoantibodies are IgG2a molecules specific for many of the autoantigens recognized by the sera of patients with systemic lupus erythematosus. In addition, MRL/lpr mice make exceedingly high titers of IgG or IgA rheumatoid factors (RF) specific for autologous IgG2a, The microenvironment of the IgG2a‐producing B cells as well as the prototypic RF autoantibodies was determined by a combination of immunohistochemical and m situ hybridization techniques. In contrast to the anti body‐producing cells present in mice responding to conventional foreign antigens, both IgG2a+ and RF+ B cells were found to be densely clustered in the T‐cell‐rich inner periarteriolar lymphatic sheath of the spleen. These results suggest that conventional antibody and autoantibody production in MRL/lpr mice may be mechanistically distinct processes.