The Autoimmune Risk Variant PTPN22 C1858T Alters B Cell Tolerance at Discrete Checkpoints and Differentially Shapes the Naive Repertoire.

ABSTRACT: A common genetic variant in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22 C1858T) has been linked to a wide range of autoimmune disorders. Although a B cell-intrinsic role in promoting disease has been reported, the mechanism(s) through which this variant functions to alter the preimmune B cell repertoire remains unknown. Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in murine Ptpn22, we show evidence for enhanced BCR, B cell-activating factor receptor, and CD40 coreceptor programs, leading to broadly enhanced positive selection of B cells at two discrete checkpoints in the bone marrow and spleen. We further identified a bias for selection of B cells into the follicular mature versus marginal

SUBMITTER: Metzler G 

PROVIDER: S-EPMC6791366 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature