التفاصيل البيبلوغرافية
| العنوان: |
Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus. |
| المؤلفون: |
Cappione, III., Amedeo1, Anolik, Jennifer H.1, Pugh-Bernard, Aimee1, Barnard, Jennifer1, Dutcher, Paul1, Silverman, Gregg2, Sanz, Iñaki1 IgnacioSanz@urmc.rochester.edu, Cappione, Amedeo 3rd3 (AUTHOR), Sanz, Iñaki (AUTHOR) |
| المصدر: |
Journal of Clinical Investigation. Nov2005, Vol. 115 Issue 11, p3205-3216. 12p. 1 Color Photograph, 1 Chart, 5 Graphs. |
| مصطلحات موضوعية: |
*SYSTEMIC lupus erythematosus, *ANTIGEN presenting cells, *VASCULAR diseases, *IMMUNE system, *IMMUNOCOMPETENT cells, *CELL populations, *AUTOANTIBODIES, *B cells, *CELL lines, *CELL physiology, *COMPARATIVE studies, *IMMUNITY, *IMMUNOGLOBULINS, *IMMUNOLOGICAL tolerance, *IMMUNOPHENOTYPING, *LYMPHOID tissue, *RESEARCH methodology, *MEDICAL cooperation, *RESEARCH, *RESEARCH funding, *RHEUMATOID arthritis, *SPLEEN, *EVALUATION research |
| مستخلص: |
Breach of B cell tolerance is central to the pathogenesis of systemic lupus erythematosus (SLE). However, how B cell tolerance is subverted in human SLE is poorly understood due to difficulties in identifying relevant autoreactive B cells and in obtaining lymphoid tissue. We have circumvented these limitations by using tonsil biopsies to study autoreactive B cells (9G4 B cells), whose regulation is abnormal in SLE. Here we show that 9G4 B cells are physiologically excluded during the early stages of the GC reaction before acquiring a centroblast phenotype. Furthermore, we provide evidence to indicate that an anergic response to B cell receptor stimulation may be responsible for such behavior. In contrast, in SLE, 9G4 B cells progressed unimpeded through this checkpoint, successfully participated in GC reactions, and expanded within the post-GC IgG memory and plasma cell compartments. The faulty regulation of 9G4 B cells was not shared by RA patients. To our knowledge, this work represents the first comparative analysis of the fate of a specific autoreactive human B cell population. The results identify a defective tolerance checkpoint that appears to be specific for human SLE. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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