Expansion of autoreactive unresponsive CD21-/low B cells in Sjögren's syndrome-associated lymphoproliferation.
Expansion of autoreactive unresponsive CD21-/low B cells in Sjögren's syndrome-associated lymphoproliferation.
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DOI：
10.1002/art.37828
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发表时间：
2013-04
影响因子：
--
通讯作者：
Cacoub, P.
中科院分区：
文献类型：
--
作者：
Saadoun, D.;Terrier, B.;Bannock, J.;Vazquez, T.;Massad, C.;Kang, I.;Joly, F.;Rosenzwajg, M.;Sene, D.;Benech, P.;Musset, L.;Klatzmann, D.;Meffre, E.;Cacoub, P.
原发性干燥综合征（pSS）是一种与非霍奇金淋巴瘤风险较高相关的自身免疫性疾病。确定pSS中驱动淋巴细胞增殖的B细胞的性质。采用流式细胞术、钙动员和基因阵列分析，分析了66例成人pSS患者[包括14例B细胞淋巴增生性疾病（LPD）患者]和30例健康供体外周血中的B细胞亚群和功能。我们通过ELISA测试了从来自pSS-LPD的单个B细胞分离的重组抗体的反应性。我们在这里报告了一个不寻常的CD 21-/低B细胞群体的扩张与淋巴细胞增生的pSS患者。pSS患者的大多数CD 21-/低B细胞表达自身反应性抗体，其识别细胞核和细胞质结构。这些B细胞属于记忆区，因为它们的免疫球蛋白基因发生了突变。它们不能诱导钙流、活化或增殖以响应B细胞受体和/或CD 40触发，表明这些自身反应性B细胞可能是无反应性的。然而，来自pSS的CD 21-/低B细胞仍然对TLR刺激有反应。CD 21-/低水平B细胞的基因阵列分析揭示了在这些B细胞中特异性表达的分子，这些分子可能诱导其无反应期。显示高频率自身反应性和无反应性CD 21-/低B细胞的pSS患者易发生淋巴细胞增生。这些细胞保留在外周血中，由功能性无反应性控制而不是被消除，并且通过TLR刺激的慢性抗原刺激可以为打破耐受性和激活这些细胞创造有利的环境。
Primary Sjögren's syndrome (pSS) is the autoimmune disease associated with the higher risk of developing non-Hodgkin lymphoma. To determine the nature of B cells driving lymphoproliferation in pSS. B cell subsets and function were analyzed in peripheral blood from 66 adult patients with pSS [including 14 patients with B-cell lymphoproliferative disorder (LPD)] and 30 healthy donors, using flow cytometry, calcium mobilization, and gene array analysis. We tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from pSS-LPD. We report here the expansion of an unusual CD21-/low B-cell population which correlates with lymphoproliferation in pSS patients. A majority of CD21–/low B cells from pSS patients expressed autoreactive antibodies, which recognized nuclear and cytoplasmic structures. These B cells belonged to the memory compartment because their immunoglobulin genes were mutated. They were unable to induce calcium flux, become activated, or proliferate in response to B-cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. However, CD21–/low B cells from pSS remained responsive to TLR stimulation. Gene array analyses of CD21–/low B cells revealed molecules specifically expressed in these B cells and that are likely to induce their unresponsive stage. pSS patients who display high frequencies of autoreactive and unresponsive CD21-/low B cells are susceptible for developing lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.
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影响因子：
3.7
作者：
Lopez F;Textoris J;Bergon A;Didier G;Remy E;Granjeaud S;Imbert J;Nguyen C;Puthier D
通讯作者：
Puthier D
影响因子：
64.5
作者：
HARTLEY, SB;COOKE, MP;GOODNOW, CC
通讯作者：
GOODNOW, CC
影响因子：
15.3
作者：
Samuels, J;Ng, YS;Meffre, E
通讯作者：
Meffre, E
影响因子：
20.3
作者：
Bahler, DW;Miklos, JA;Swerdlow, SH
通讯作者：
Swerdlow, SH
影响因子：
45.3
作者：
Harris, NL;Jaffe, ES;Bloomfield, CD
通讯作者：
Bloomfield, CD