Positive Selection of Anti–Thy-1 Autoreactive B-1 Cells and Natural Serum Autoantibody Production Independent from Bone Marrow B Cell Development
| Autor: | Susan A. Shinton, Ming Gui, Richard R. Hardy, Joni Dashoff, Masanao Asano, Kyoko Hayakawa, Lijun Wen |
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| Rok vydání: | 2003 |
| Předmět: |
IgM
Immunology B-cell receptor B-Lymphocyte Subsets Bone Marrow Cells CD5 Antigens Autoantigens Article Immunophenotyping Immune tolerance Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Immune Tolerance medicine Animals Immunology and Allergy B-1 Thy-1 B cell Autoantibodies 030304 developmental biology ATA 0303 health sciences biology Autoantibody Cell Differentiation Flow Cytometry CD5 medicine.anatomical_structure Immunoglobulin M Splenectomy biology.protein Thy-1 Antigens Bone marrow Spleen 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20021459 |
| Popis: | A natural serum autoantibody specific for the Thy-1 glycoprotein (anti-Thy-1 autoantibody [ATA]) is produced by B-1 cells that are positively selected by self-antigen. Here, using ATA micro kappa transgenic mice we show that cells with this B cell receptor are negatively selected during bone marrow (BM) development. In a Thy-1 null environment, BM ATA B cells progress to a normal follicular stage in spleen. However, in a self-antigen-positive environment, development is arrested at an immature stage in the spleen, concomitant with induction of CD5. Such cells are tolerant and short-lived, different from B-1. Nonetheless, ATA-positive selection was evident by self-antigen-dependent high serum ATA production, comprising approximately 90% of serum immunoglobulin M in ATA micro kappa mice. Splenectomy did not eliminate ATA production and transfer of tolerant splenic B cells did not induce it. These findings demonstrate that B-1 positive selection, resulting in the production of natural serum ATA, arises independently from the major pathway of BM B cell development and selection. |
| Databáze: | OpenAIRE |
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