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The mechanistic links between genetic variation and autoantibody production in autoimmune disease remain obscure. Autoimmune lymphoproliferative syndrome (ALPS) is caused by inactivating mutations in FAS or FASL, with autoantibodies thought to arise through failure of FAS-mediated removal of self-reactive germinal center (GC) B cells. Here we show that FAS is in fact not required for this process...
Secondary diversification of the B cell repertoire by immunoglobulin gene somatic hypermutation in the germinal center (GC) is essential for providing the high-affinity antibody specificities required for long-term humoral immunity. While the risk to self-tolerance posed by inadvertent generation of self-reactive GC B cells has long been recognized, it has not previously been possible to identify...
Summary: Interactions between B‐cell antigen receptors (BCRs) and their ligands have a complexity and variability that is unparalleled within known biology. Each developing B cell undergoes gene rearrangements to generate a BCR encoded by a unique pair of immunoglobulin (Ig) variable region genes, which serves to make the antigen‐binding capabilities of primary BCRs incredibly diverse. Further diversification...
Summary: Targeted modification of the mouse genome provides the capability to manipulate complex physiological processes in a precise and controlled manner. Investigation of B‐lymphocyte biology has benefited not only from the targeted modification of genes controlling B‐cell survival and responsiveness, but also from the manipulation of antigen specificity made possible by targeting endogenous immunoglobulin...
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