Altered B cell receptor signaling in human systemic lupus erythematosus.
Regulation of B cell receptor signaling is essential for the development of specific immunity while retaining tolerance to self. Systemic lupus erythematosus (SLE) is characterized by a loss of B cell tolerance and the production of anti-self antibodies. Accompanying this break down in tolerance are alterations in B cell receptor signal transduction including elevated induced calcium responses and increased protein phosphorylation. Specific pathways that negatively regulate B cell signaling have been shown to be impaired in some SLE patients. These patients have reduced levels of the kinase Lyn in lipid raft microdomains and this reduction is inversely correlated with increased CD45 in lipid rafts. Function and expression of the inhibitory immunoglobulin receptor FcgammaRIIB is also reduced in Lupus IgM- CD27+ memory cells. Because the relative contribution of different memory and transitional B cell subsets can be abnormal in SLE patients, we believe studies targeted to well defined B cell subsets will be necessary to further our understanding of signaling abnormalities in SLE. Intracellular flow cytometric analysis of signaling is a useful approach to accomplish this goal.
Jenks
Scott A
SA
Department of Medicine, Division of Allergy, Immunology and Rheumatology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, New York 14642, USA.
Sanz
Iñaki
I
D001323:Autoantibodies / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002469:Cell Separation / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007156:Immunologic Memory; D050356:Lipid Metabolism / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017634:Self Tolerance; D015398:Signal Transduction; D019061:src-Family Kinases / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; C499173:FCGR2B protein, human; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases