Immune complexes present in the sera of autoimmune mice activate rheumatoid factor B cells

IR Rifkin, EA Leadbetter, BC Beaudette… - The Journal of …, 2000 - journals.aai.org
IR Rifkin, EA Leadbetter, BC Beaudette, C Kiani, M Monestier, MJ Shlomchik
The Journal of Immunology, 2000journals.aai.org
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 (IgG2a j), 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 …
Abstract
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 (IgG2a j), 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 IgG2a j, but the IgG2a j was stimulatory only when in the form of immune complexes. Monomeric IgG2a j 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.
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