학술논문
Themis2 lowers the threshold for B cell activation during positive selection
Document Type
Report
Author
Cheng, Daian; Deobagkar-Lele, Mukta; Zvezdova, Ekaterina; Choi, Seeyoung; Uehara, Shoji; Baup, Delphine; Bennett, Sophia C; Bull, Katherine R; Crockford, Tanya L; Ferry, Helen; Warzecha, Claude; Marcellin, Marlène; de Peredo, Anne Gonzalez; Lesourne, Renaud; Anzilotti, Consuelo; Love, Paul E; Cornall, Richard J
Source
Nature Immunology. February 2017, Vol. 18 Issue 2, p205, 9 p.
Subject
Language
English
ISSN
1529-2908
Abstract
Author(s): Daian Cheng [1]; Mukta Deobagkar-Lele [1]; Ekaterina Zvezdova [2]; Seeyoung Choi [2]; Shoji Uehara [2]; Delphine Baup [1]; Sophia C Bennett [1]; Katherine R Bull [1]; Tanya L Crockford [...]
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.
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.