Journal
NATURE IMMUNOLOGY
Volume 18, Issue 2, Pages 205-213Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3642
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Funding
- Medical Research Council
- Intramural Research Program of the Eunice Kennedy Shriver, NICHD (PEL: project) [1ZIAHD001803-19]
- Wellcome Trust
- MRC [MC_UU_00008/6, MC_UU_12010/6] Funding Source: UKRI
- Medical Research Council [MC_UU_00008/6, MC_UU_12010/6] Funding Source: researchfish
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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 gamma 2 (PLC-gamma 2), and increased activation of PLC-gamma 2 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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