Unexpected autoantibody production in membrane Ig-mu-deficient/lpr mice.
In the B lymphocyte lineage, Fas-mediated cell death is important in controlling activated mature cells, but little is known about possible functions at earlier developmental stages. In this study we found that in mice lacking the IgM transmembrane tail exons (muMT mice), in which B cell development is blocked at the pro-B stage, the absence of Fas or Fas ligand allows significant B cell development and maturation, resulting in high serum Ig levels. These B cells demonstrate Ig heavy chain isotype switching and autoimmune reactivity, suggesting that lack of functional Fas allows maturation of defective and/or self-reactive B cells in muMT/lpr mice. Possible mechanisms that may allow maturation of these B cells are discussed.
Melamed
D
D
Faculty of Medicine, Department of Immunology, Technion, Haifa, Israel. Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA. melamedd@techunix.technion.ac.il
Miri
E
E
Leider
N
N
Nemazee
D
D
D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics*; D007136:Immunoglobulins / Q000096:biosynthesis; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008206:Lymphatic Diseases / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr / Q000235:genetics* / Q000276:immunology*; D008817:Mice, Mutant Strains; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D019014:fas Receptor / Q000502:physiology
D001323:Autoantibodies; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor