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Examination of Thymic Positive and Negative Selection by Flow Cytometry
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Themis2 lowers the threshold for B cell activation during positive selection

Daian Cheng1, Mukta Deobagkar-Lele1, Ekaterina Zvezdova2

  • 1MRC Human Immunology Unit, Weatherall Institute for Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Nature Immunology
|December 20, 2016
PubMed

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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