Themis2 lowers the threshold for B cell activation during positive selection

• Published in: Nature immunology Vol. 18; no. 2; pp. 205 - 213
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-02-2017; Nature Publishing Group
• Subjects: 631/250/1619/40; 631/250/2152/2153; Adaptive Immunity; Animals; B cells; B-Lymphocytes - physiology; Biomedicine; Cell Differentiation; Cell Lineage; Cells, Cultured; Cellular proteins; Cellular signal transduction; Clonal Selection, Antigen-Mediated; Genetic aspects; Germinal Center - immunology; GRB2 Adaptor Protein - metabolism; Health aspects; Immune response regulation; Immunology; Infectious Diseases; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Life Sciences; Lymphocyte Activation; Lymphocytes; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Phospholipase C gamma - metabolism; Receptors, Antigen, B-Cell - metabolism; Self Tolerance; src-Family Kinases - metabolism
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3642

Cornall and colleagues show that Themis2 interacts with the phospholipase PLC-γ2 and lowers the threshold for B cell activation by low but not high avidity antigens.
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.