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- W642999265 abstract "Abstract The pro-survival cytokine BAFF was recently proposed to regulate peripheral immunological tolerance within the B cell lineage. Studies conducted in two different model systems of B cell autoimmunity demonstrated a selective elimination of autoreactive B cells upon BAFF depletion. These observations led to a model positing a higher dependency of autoreactive B cells on BAFF. We tested this model by exploiting our experimental system in which targeted Ig heavy chain knock-in transgenic mice (HKI) produce large numbers of B cells that are dually reactive to foreign (Ars) and self (DNA) antigens. HKI B cells do not exhibit the classical features of anergy, escape central tolerance mechanisms, and gain access to normal follicular locales. We show that mature, naïve, autoreactive HKI B cells are out-competed in the presence of a polyclonal repertoire. However, this is not due to a higher dependency of HKI B cells on BAFF for survival. In addition, excess BAFF does not rescue HKI B cells from selective elimination. These findings suggest that some autoreactive B cells can fully develop while in competition with non-autoreactive cells for normal levels of BAFF, but remain at a competitive disadvantage for other trophic factors that regulate peripheral stability. As such, our data indicate the existence of parallel peripheral tolerogenic mechanisms that may act through BCR signaling and at further stages of differentiation such as those that take place in germinal centers." @default.
- W642999265 created "2016-06-24" @default.
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- W642999265 date "2010-04-01" @default.
- W642999265 modified "2023-09-27" @default.
- W642999265 title "Self reactive B cells that do not exhibit higher BAFF dependency for survival (143.42)" @default.
- W642999265 doi "https://doi.org/10.4049/jimmunol.184.supp.143.42" @default.
- W642999265 hasPublicationYear "2010" @default.
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