title: Negative selection of self-reactive chicken B cells requires B cell receptor signaling and is independent of the bursal microenvironment.
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.
authors: Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada;
authors: Dariush
authors: D
authors: Davani
authors: Zeev
authors: Z
authors: Pancer
authors: Hilde
authors: H
authors: Cheroutre
authors: Michael J H
authors: MJ
authors: Ratcliffe
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D030161:Avian Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002060:Bursa of Fabricius / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051925:CD79 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D060833:Cellular Microenvironment / Q000276:immunology*; D002642:Chick Embryo; D002645:Chickens; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007798:Lampreys / Q000235:genetics / Q000276:immunology; D051379:Mice; D009113:Muramidase / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011946:Receptors, Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D001324:Autoantigens; D030161:Avian Proteins; D051925:CD79 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; D007075:Immunoglobulin M; D011946:Receptors, Antigen; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; C421864:hen egg lysozyme; D009113:Muramidase