دورية أكاديمية
Reduced receptor editing in lupus-prone MRL/lpr mice.
| العنوان: | Reduced receptor editing in lupus-prone MRL/lpr mice. |
|---|---|
| المؤلفون: | Lamoureux JL; Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA., Watson LC, Cherrier M, Skog P, Nemazee D, Feeney AJ |
| المصدر: | The Journal of experimental medicine [J Exp Med] 2007 Nov 26; Vol. 204 (12), pp. 2853-64. Date of Electronic Publication: 2007 Oct 29. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Rockefeller University Press |
| مواضيع طبية MeSH: | Lupus Erythematosus, Systemic/*genetics , RNA Editing/*genetics , Receptors, Antigen, B-Cell/*genetics, Animals ; B-Lymphocytes/immunology ; Bone Marrow Cells/immunology ; Bone Marrow Cells/physiology ; Cells, Cultured ; Genetic Predisposition to Disease ; Interleukin-7/physiology ; Mice ; Mice, Inbred MRL lpr ; Mice, Inbred Strains ; Mice, Transgenic ; Polymerase Chain Reaction ; Receptors, Antigen, B-Cell/physiology |
| مستخلص: | The initial B cell repertoire contains a considerable proportion of autoreactive specificities. The first major B cell tolerance checkpoint is at the stage of the immature B cell, where receptor editing is the primary mode of eliminating self-reactivity. The cells that emigrate from the bone marrow have a second tolerance checkpoint in the transitional compartment in the spleen. Although it is known that the second checkpoint is defective in lupus, it is not clear whether there is any breakdown in central B cell tolerance in the bone marrow. We demonstrate that receptor editing is less efficient in the lupus-prone strain MRL/lpr. In an in vitro system, when receptor-editing signals are given to bone marrow immature B cells by antiidiotype antibody or after in vivo exposure to membrane-bound self-antigen, MRL/lpr 3-83 transgenic immature B cells undergo less endogenous rearrangement and up-regulate recombination activating gene messenger RNA to a lesser extent than B10 transgenic cells. CD19, along with immunoglobulin M, is down-regulated in the bone marrow upon receptor editing, but the extent of down-regulation is fivefold less in MRL/lpr mice. Less efficient receptor editing could allow some autoreactive cells to escape from the bone marrow in lupus-prone mice, thus predisposing to autoimmunity. |
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| معلومات مُعتمدة: | R01 AI61167 United States AI NIAID NIH HHS; T32 HL007195 United States HL NHLBI NIH HHS; T32 HL07195 United States HL NHLBI NIH HHS; R01 AI033608 United States AI NIAID NIH HHS; R01 AI061167 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Interleukin-7) 0 (Receptors, Antigen, B-Cell) |
| تواريخ الأحداث: | Date Created: 20071031 Date Completed: 20071214 Latest Revision: 20211020 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC2118512 |
| DOI: | 10.1084/jem.20071268 |
| PMID: | 17967905 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1540-9538 |
|---|---|
| DOI: | 10.1084/jem.20071268 |