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.
Journal article
2017-02-01T00:00:00+00:00
18
205 - 213
8
Adaptive Immunity, Animals, B-Lymphocytes, Cell Differentiation, Cell Lineage, Cells, Cultured, Clonal Selection, Antigen-Mediated, GRB2 Adaptor Protein, Germinal Center, Intracellular Signaling Peptides and Proteins, Lymphocyte Activation, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Phospholipase C gamma, Receptors, Antigen, B-Cell, Self Tolerance, src-Family Kinases