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Immunologic Research, 2007
The appearance of autoantibodies in autoimmune diseases such as lupus suggests that B-cell tolera... more 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 Bcell 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. Keywords Tolerance Á Immunoglobulin Á BCR Á Transgenic Á Autoimmunity Á Lupus Á Receptor editing Á Deletion Á Anergy One of the key functions of the immune system is to maintain tolerance to self i.e., to not generate responses to the body's own tissues. Although the frequency of generation of selfreactive Band T-lymphocytes by random primary receptor rearrangement is high, the immune system has evolved a series of tolerance checkpoints to ensure that self-reactive Band T-cells generated in the bone marrow or thymus do not enter the peripheral circulating pool, or if they do enter are effectively rendered functionally inactive. However, when such mechanisms fail it leads to the 'recognition of self' or 'horror autotoxicus'. B-cells, an important arm of the adaptive immune system, play a vital role in the maintenance of
Immunologic Research, 2007
The appearance of autoantibodies in autoimmune diseases such as lupus suggests that B-cell tolera... more 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 Bcell 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. Keywords Tolerance Á Immunoglobulin Á BCR Á Transgenic Á Autoimmunity Á Lupus Á Receptor editing Á Deletion Á Anergy One of the key functions of the immune system is to maintain tolerance to self i.e., to not generate responses to the body's own tissues. Although the frequency of generation of selfreactive Band T-lymphocytes by random primary receptor rearrangement is high, the immune system has evolved a series of tolerance checkpoints to ensure that self-reactive Band T-cells generated in the bone marrow or thymus do not enter the peripheral circulating pool, or if they do enter are effectively rendered functionally inactive. However, when such mechanisms fail it leads to the 'recognition of self' or 'horror autotoxicus'. B-cells, an important arm of the adaptive immune system, play a vital role in the maintenance of