Defective isotype-specific regulation of IgA anti-erythrocyte autoantibody-forming cells in NZB mice.
B cell hyperactivity characterizes many autoimmune diseases. In NZB mice this is manifested by a variety of immunologic aberrations, including increased B cell proliferation and hyper IgM and IgA secretion in vitro. Recent studies have shown that IgA secretion can be suppressed or enhanced in an isotype-specific manner by a soluble factor(s), called IgA-binding factor (IgABF), produced by IgA FcR-bearing T cells. We now show that T cells from young NZB mice, cultured with high concentrations of IgA, produce an IgABF that has aberrant biologic activity when compared to IgABF produced from IgA FcR+ T cells of BALB/c mice. Although BALB/c IgABF normally suppresses proliferation and secretion by IgA-producing B cells, neither proliferation nor IgA secretion from normal murine IgA-B cells is suppressed by NZB IgABF. In fact, IgA secretion is significantly enhanced by NZB IgABF. We also present the first evidence of IgA anti-mouse erythrocyte (anti-MRBC) autoantibody-forming cells present in the spleens of NZB mice. Whereas BALB/c IgABF suppresses the in vitro generation of IgA anti-MRBC autoantibody-forming cells by NZB spleen cells, NZB IgABF enhances this response. Of particular interest is the development of IgA anti-MRBC autoantibody-forming cells in cultures of spleen cells from nonautoimmune BALB/c mice in the presence of NZB IgABF. These studies suggest that isotype-specific T cells factors might play an important role in the development of autoantibody-forming cells.
Moore
J S
JS
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6082.
Hoover
R G
RG
D000818:Animals; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001789:Blood Group Antigens / Q000276:immunology*; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000378:metabolism; D007132:Immunoglobulin Isotypes / Q000172:deficiency*; D007166:Immunosuppressive Agents / Q000502:physiology; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010641:Phenotype; D029584:Prostatic Secretory Proteins; D011961:Receptors, Fc; D013601:T-Lymphocytes / Q000145:classification / Q000378:metabolism
D015703:Antigens, CD; D001323:Autoantibodies; D001789:Blood Group Antigens; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D007166:Immunosuppressive Agents; D008222:Lymphokines; D029584:Prostatic Secretory Proteins; D011961:Receptors, Fc; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors