Splenic proliferative lymphoid nodules distinct from germinal centers are sites of autoantigen stimulation in immune thrombocytopenia
Splenic proliferative lymphoid nodules distinct from germinal centers are sites of autoantigen stimulation in immune thrombocytopenia
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DOI：
10.1182/blood-2012-04-424648
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发表时间：
2012-12-13
期刊：
影响因子：
20.3
通讯作者：
Doerner, Thomas
中科院分区：
文献类型：
--
作者：
Daridon, Capucine;Loddenkemper, Christoph;Doerner, Thomas
为了了解体液自身免疫的更多特异性异常，我们研究了31个免疫性血小板减少症(ITP)患者的脾和36个对照脾。详细的分析确定了至少两种不同的脾结构，包括增殖的B细胞、经典的生发中心(GC)和增殖的淋巴结节(PLN)。PLN的特点是增殖的Ki67(+)B细胞靠近滤泡树突状细胞(FDCs)，缺乏极化进入暗区和亮区。与GC中的细胞不同，PLN中增殖的B细胞缺乏bcl6的表达。在ITP脾的PLN和GCs中，T细胞密度均显著降低。在ITP脾的PLN中，T滤泡辅助细胞(T-FH)和调节性T细胞均减少，表明T细胞控制的丧失导致了耐受性缺陷。在ITP患者的PLN中，发现与FDCs紧密结合的IgM免疫复合物中含有丰富的血小板膜糖蛋白(GP)IIb/IIIa自身抗原，接近于增殖的B细胞。GPIV的出现频率较低，但与GPIIb/IIIa的PLN不同。在ITP组和对照组的GC中未发现自身抗原，提示PLN是ITP中自身抗原刺激的部位，可能与T细胞和/或现有自身抗原的缺乏控制有关。(血。2012；120(25)：5021-5031)
To understand more specific abnormalities of humoral autoimmunity, we studied 31 spleens from immune thrombocytopenia (ITP) patients and 36 control spleens. Detailed analysis identified at least 2 different splenic structures accommodating proliferating B cells, classic germinal centers (GCs), and proliferative lymphoid nodules (PLNs). PLNs were characterized by proliferating Ki67(+) B cells close to follicular dendritic cells (FDCs) and lacked polarization into dark and light zones. As opposed to cells in GCs, proliferating B cells in PLN lacked expression of Bcl6. In both PLNs and GCs of ITP spleens, the density of T cells was significantly reduced. Both T follicular helper cells (T-FH) and regulatory T cells were reduced within PLNs of ITP spleens suggesting a defect of tolerance related to a loss of T-cell control. Within PLNs of ITP, but not controls, abundant platelet glycoprotein (GP) IIb/IIIa autoantigens was found in IgM containing immune complexes tightly bound to FDCs and closely approximated to proliferating B cells. GPIV was found less often, but not in the same PLNs as GPIIb/IIIa. Autoantigens were not found in the GCs of ITP or controls indicating that PLNs are the sites of autoantigen stimulation in ITP potentially related to a lack of control by T cells and/or the present autoantigen. (Blood. 2012; 120(25): 5021-5031)