Person: Al Qureshah, Fahd
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Al Qureshah
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Fahd
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Al Qureshah, Fahd
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Publication Endogenous B Cells Outcompeting Autoreactive Knock-in B Cells in Germinal Centers of Lupus Mice(2016-05-24) Al Qureshah, Fahd; Carroll, Michaell; Degn, SorenSystemic lupus erythematosus (SLE) is characterized by the production of autoantibodies against nucleic acid antigens. Despite the recent insight into the pathogenesis of the disease, the exact underlying causes of B cell autoreactivity in SLE remain largely unknown. Using a knock in mouse model, we were able to follow the evolution of autoreactive germinal centers (GCs) in a BCR knock-in Aicda Cre/ERT2 stop-flox-EYFP mouse strain. In this knock-in mouse, a low frequency of emergent autoreactive B cells breaks follicular exclusion and form GCs. Interestingly; we observed that the composition of the GCs appears to change with preferential expansion of diverse non-knock-in derived clones as GCs mature. Our findings have been elucidated through different approaches, including flow cytometry, histology, bone marrow chimera, and sequencing. Also, YFP+ memory B cells were tracked to 90 days after tamoxifen administration and, during this time, persistent GC cells seemed to continuously diversify their B cell receptors. Adoptive transfer of YFP+ cells into revealed that they are engaged into the spontaneous GCs in the knock-in mice. Analysis of many of sequences revealed the prevalence of basic amino acids in CRD regions suggesting autoreactivity against nuclear antigens. These observations inevitably have implications on our understanding of the pathological processes of epitope spreading commonly observed in lupus and similar autoimmune diseases.