1. Negative selection of self-reactive chicken B cells requires B cell receptor signaling and is independent of the bursal microenvironment.
- Author
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Davani D, Pancer Z, Cheroutre H, and Ratcliffe MJ
- Subjects
- Animals, Autoantigens metabolism, Avian Proteins genetics, Avian Proteins metabolism, B-Lymphocytes metabolism, Bursa of Fabricius cytology, Bursa of Fabricius immunology, Bursa of Fabricius metabolism, CD79 Antigens genetics, CD79 Antigens immunology, CD79 Antigens metabolism, CD8 Antigens genetics, CD8 Antigens immunology, CD8 Antigens metabolism, Cell Line, Tumor, Cells, Cultured, Chick Embryo, Chickens, Fibroblasts cytology, Fibroblasts immunology, Fibroblasts metabolism, Flow Cytometry, Immunoglobulin M genetics, Immunoglobulin M immunology, Immunoglobulin M metabolism, Lampreys genetics, Lampreys immunology, Mice, Muramidase immunology, Protein Binding immunology, Receptors, Antigen genetics, Receptors, Antigen immunology, Receptors, Antigen metabolism, Receptors, Antigen, B-Cell genetics, Receptors, Antigen, B-Cell metabolism, Receptors, Fc genetics, Receptors, Fc immunology, Receptors, Fc metabolism, Autoantigens immunology, Avian Proteins immunology, B-Lymphocytes immunology, Cellular Microenvironment immunology, Receptors, Antigen, B-Cell immunology, Signal Transduction immunology
- Abstract
Although the negative selection of self-reactive B cells in the bone marrow of mammals has been clearly demonstrated, it remains unclear in models of gut-associated B cell lymphopoiesis, such as that of the chicken (Gallus gallus). We have generated chicken surface IgM-related receptors in which the diversity region of the lamprey variable lymphocyte receptor (VLR) has been fused to the C region of chicken surface IgM (Tμ). Expression of a VLR:Tμ receptor with specificity for PE supported normal development of B cells, whereas a VLR:Tμ receptor specific to hen egg lysozyme (a self-antigen with respect to chicken B cells) induced, in vivo, complete deletion of VLR(HEL)Tμ-expressing B cells. In ovo i.v. injection of PE resulted in deletion of VLR(PE)Tμ-expressing Β cells in the embryo spleen, demonstrating that negative selection was independent of the bursal microenvironment. Although chickens transduced with a murine CD8α:chicken Igα fusion protein contained B cells expressing mCD8α:chIgα, cotransfection of the mCD8α:chIgα construct, together with thymus leukemia Ag (a natural ligand for mCD8α), resulted in reduced levels of mCD8α:chIgα-expressing B cells in inverse proportion to the levels of thymus leukemia Ag-expressing cells. Deletion of mCD8α:chIgα-expressing cells was specific for B cells and required active signaling downstream of the mCD8α:chIgα receptor. Ag-mediated negative selection of developing chicken B cells can therefore occur independently of the bursal microenvironment and is dependent on signaling downstream of the BCR.
- Published
- 2014
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