Understanding B-cell tolerance through the use of immunoglobulin transgenic models.
The appearance of autoantibodies in autoimmune diseases such as lupus suggests that B-cell tolerance to self is breached. Hence it becomes important to unravel the precise cellular and molecular mechanisms that are responsible for violations in various B-cell tolerance checkpoints in autoimmune diseases. B-cell immunoglobulin or B-cell receptor transgenic models have been of immense aid in uncovering many of these key tolerance checkpoints during normal B-cell development. By breeding these transgenic models onto mice that are engineered to lack or hyperexpress various B-cell molecules, including signaling intermediates, researchers have delineated the role of these molecules in B-cell tolerance. These transgenic models have also been useful in delineating the impact of various lupus prone genomes and lupus susceptibility loci on B-cell tolerance. This review focuses on some of the more well-studied B-cell receptor transgenic models and the lessons they have taught us over the past two decades.
Kumar
Kirthi Raman
KR
Department of Internal Medicine/Rheumatology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8884, USA. Kirthi.raman@utsouthwestern.edu
Mohan
Chandra
C
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; C421864:hen egg lysozyme; D009113:Muramidase