Immune complexes present in the sera of autoimmune mice activate rheumatoid factor B cells.
The fate of an autoreactive B cell is determined in part by the nature of the interaction of the B cell receptor with its autoantigen. In the lpr model of systemic autoimmunity, as well as in certain human diseases, autoreactive B cells expressing rheumatoid factor (RF) binding activity are prominent. A murine B cell transgenic model in which the B cell receptor is a RF that recognizes IgG2a of the j allotype (IgG2aj), but not the b allotype, was used in this study to investigate how the form of the autoantigen influences its ability to activate B cells. We found that sera from autoimmune mice, but not from nonautoimmune mice, were able to induce the proliferation of these RF+ B cells but did not stimulate B cells from RF- littermate controls. The stimulatory factor in serum was found to be IgG2aj, but the IgG2aj was stimulatory only when in the form of immune complexes. Monomeric IgG2aj failed to stimulate. Immune complexes containing lupus-associated nuclear and cytoplasmic autoantigens were particularly potent B cell activators in this system. Appropriate manipulation of such autoantibody/autoantigen complexes may eventually provide a means for therapeutic intervention in patients with certain systemic autoimmune disorders.
Rifkin
I R
IR
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
Leadbetter
E A
EA
Beaudette
B C
BC
Kiani
C
C
Monestier
M
M
Shlomchik
M J
MJ
Marshak-Rothstein
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000378:metabolism / Q000502:physiology*; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D053222:Fas Ligand Protein; D006241:Haptens / Q000276:immunology; D006650:Histocompatibility Testing; D006358:Hot Temperature; D007106:Immune Sera / Q000494:pharmacology; D007126:Immunoglobulin Allotypes / Q000235:genetics / Q000502:physiology; D007074:Immunoglobulin G / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009707:Nucleosomes / Q000276:immunology; D012217:Rheumatoid Factor / Q000096:biosynthesis / Q000378:metabolism*; D019014:fas Receptor / Q000235:genetics
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006241:Haptens; D007106:Immune Sera; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009707:Nucleosomes; D019014:fas Receptor; D012217:Rheumatoid Factor