Sening Wolfgang, Lisner Renate, Niedobitek Gerald
Institute for Pathology, Friedrich-Alexander-University, Krankenhausstr. 8-10, 91054, Erlangen, Germany.
J Autoimmun. 2004 Mar;22(2):147-52. doi: 10.1016/j.jaut.2003.12.002.
It has been suggested that recombination activating gene (RAG)-dependent revision of the immunoglobulin genes in germinal centres may contribute to local production of autoantibodies in Hashimoto thyroiditis (HT) and rheumatoid arthritis (RA). To test this hypothesis we examined HT and RA tissues for expression of RAG and terminal deoxynucleotidyl transferase (TdT) in situ. Paraffin-embedded tissues from 19 HT patients and from 20 RA patients were subjected to immunohistochemistry using TdT-specific antibodies. Expression of the RAGs was studied by in situ hybridisation. Tonsil sections were used as a control. Expression of TdT and RAGs was detected in extrafollicular lymphocytes in control tonsil sections. By contrast, only rare TdT-expressing cells were identified in 11 of 19 HT and in 2 of 20 RA samples. Germinal centre B-cells were consistently TdT- and RAG-negative. These results suggest that local RAG-dependent receptor revision in germinal centres is unlikely to contribute to production of autoantibodies in HT and RA. The presence of TdT-positive extrafollicular cells may represent an influx of immature cells in the context of chronic immune stimulation.
有人提出,生发中心免疫球蛋白基因的重组激活基因(RAG)依赖性修正可能有助于桥本甲状腺炎(HT)和类风湿性关节炎(RA)中自身抗体的局部产生。为了验证这一假设,我们检测了HT和RA组织中RAG和末端脱氧核苷酸转移酶(TdT)的原位表达。使用TdT特异性抗体对19例HT患者和20例RA患者的石蜡包埋组织进行免疫组织化学检测。通过原位杂交研究RAG的表达。扁桃体切片用作对照。在对照扁桃体切片的滤泡外淋巴细胞中检测到TdT和RAG的表达。相比之下,在19例HT患者中的11例和20例RA样本中的2例中仅鉴定出罕见的TdT表达细胞。生发中心B细胞始终为TdT和RAG阴性。这些结果表明,生发中心局部RAG依赖性受体修正不太可能导致HT和RA中自身抗体的产生。TdT阳性滤泡外细胞的存在可能代表在慢性免疫刺激情况下未成熟细胞的流入。