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Nat Immunol. 2017 Feb;18(2):205-213. doi: 10.1038/ni.3642. Epub 2016 Dec 19.

Themis2 lowers the threshold for B cell activation during positive selection.

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MRC Human Immunology Unit, Weatherall Institute for Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Institut de Pharmacologie et de Biologie Structurale and Université de Toulouse, Université Paul Sabatier, Centre National de la Recherche Scientifique, Toulouse, France.
Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; and Institut National de la Santé et de la Recherche Médicale, U1043, Centre National de la Recherche Scientifique, and Université de Toulouse, Université Paul Sabatier, Toulouse, France.


The positive and negative selection of lymphocytes by antigen is central to adaptive immunity and self-tolerance, yet how this is determined by different antigens is not completely understood. We found that thymocyte-selection-associated family member 2 (Themis2) increased the positive selection of B1 cells and germinal center B cells by self and foreign antigens. Themis2 lowered the threshold for B-cell activation by low-avidity, but not high-avidity, antigens. Themis2 constitutively bound the adaptor protein Grb2, src-kinase Lyn and signal transducer phospholipase γ2 (PLC-γ2), and increased activation of PLC-γ2 and its downstream pathways following B cell receptor stimulation. Our findings identify a unique function for Themis2 in differential signaling and provide insight into how B cells discriminate between antigens of different quantity and quality.

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