UNIQUE SITE OF IGG2A AND RHEUMATOID-FACTOR PRODUCTION IN MRL LPR MICE/

MRL/lpr (Fas-deficient) mice develop an autoimmune syndrome associated . with excessive production of autoantibodies. A significant portion o f these autoantibodies are IgG2a molecules specific for many of the au toantigens recognized by the sera of patients with systemic lupus eryt hematosus. In addition, MRL/lpr mice make exceedingly high titers of I gG or IgA rheumatoid factors (RF) specific for autologous IgG2a, The m icroenvironment of the IgG2a-producing B cells as well as the prototyp ic RF autoantibodies was determined by a combination of immunohistoche mical and in situ hybridization techniques. In contrast to the antibod y-producing cells present in mice responding to conventional foreign a ntigens, both IgG2a(+) and RF+ B cells were found to be densely cluste red in the T-cell-rich inner periarteriolar lymphatic sheath of the sp leen. These results suggest that conventional antibody and autoantibod y production in MRL/lpr mice may be mechanistically distinct processes .