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 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 in situ hybridization techniques. In contrast to the antibody-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.
Jacobson
B A
BA
Genetics Institute, Cambridge, Massachusetts, USA.
Rothstein
T L
TL
Marshak-Rothstein
A
A
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D012217:Rheumatoid Factor / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology; D019014:fas Receptor / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D019014:fas Receptor; D012217:Rheumatoid Factor