Lupus-Specific Antiribonucleoprotein B Cell Tolerance in Nonautoimmune Mice Is Maintained by Differentiation to B-1 and Governed by B Cell Receptor Signaling Thresholds

• Published in: The Journal of immunology (1950) 2001-02, Vol.166 (4), p.2412-2419
• Main Authors: Qian, Ye, Santiago, Carlos, Borrero, Michelle, Tedder, Thomas F, Clarke, Stephen H
• Format: Article
• Language: English
• Subjects: AB-1 cells; Animals; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, CD19 - biosynthesis; Antigens, CD19 - genetics; Antigens, Differentiation, B-Lymphocyte - biosynthesis; Antigens, Differentiation, B-Lymphocyte - genetics; Autoantibodies - blood; Autoantibodies - physiology; Autoantigens - immunology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; Cell Adhesion Molecules; Cell Differentiation - genetics; Cell Differentiation - immunology; Immune Tolerance - genetics; Lectins; Lupus Erythematosus, Systemic - immunology; Mice; Mice, Inbred MRL lpr; Mice, Knockout; Mice, Transgenic; Peritoneum - cytology; Peritoneum - immunology; Receptors, Antigen, B-Cell - biosynthesis; Receptors, Antigen, B-Cell - physiology; ribonucleoprotein Sm; Ribonucleoproteins, Small Nuclear - immunology; Sialic Acid Binding Ig-like Lectin 2; Signal Transduction - genetics; Signal Transduction - immunology; snRNP Core Proteins; Spleen - cytology; Spleen - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.4.2412

Systemic lupus erythematosus is an autoimmune disease characterized by the presence of autoantibodies. One of the unique targets of the immune system in systemic lupus erythematosus is Sm, a ribonucleoprotein present in all cells. To understand the regulation of B cells specific to the Sm Ag in normal mice, we have generated an Ig H chain transgenic mouse (2-12H Tg). 2-12H Tg mice produce B cells specific for the Sm that remain tolerant due to ignorance. We demonstrate here that anti-Sm B cells of 2-12H Tg mice can differentiate into Sm-specific peritoneal B-1 cells that remain tolerant. Differentiation to B-1 and tolerance are governed by the strength of B cell receptor signaling, since manipulations of the B cell receptor coreceptors CD19 and CD22 affect anti-Sm B cell differentiation and autoantibody production. These results suggest a differentiation scheme in which peripheral ignorance to Sm is maintained in mice by the differentiation of anti-Sm B cells to B-1 cells that have increased activation thresholds.