A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi.
A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi.
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DOI：
10.1084/jem.20121801
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发表时间：
2013-01-14
期刊：
影响因子：
--
通讯作者：
van Noesel CJ
中科院分区：
文献类型：
--
作者：
Hoogeboom R;van Kessel KP;Hochstenbach F;Wormhoudt TA;Reinten RJ;Wagner K;Kater AP;Guikema JE;Bende RJ;van Noesel CJ
具有IGHV基因突变的慢性淋巴细胞白血病的一个亚群表达酵母和丝状真菌抗原决定簇β-(1，6)-葡聚糖的BCR。B细胞慢性淋巴细胞白血病(CLL)是成人最常见的白血病，是CD5+CD19+B淋巴细胞的克隆性扩增。两种类型的CLL被区分为携带未突变或体细胞突变的免疫球蛋白(IGs)，分别与不良预后和良好预后相关。超过30%的CLL可以根据其刻板的B细胞受体(BCR)的表达进行分组，这强烈表明独特的抗原参与了CLL的发展。未突变的CLL以种系结构携带Ig重链可变(IGHV)基因，表达低亲和力、多聚和自我反应的BCR。然而，IGHV基因突变的CLL(M-CLL)的抗原性尚不清楚。在这项研究中，我们描述了一个新的M-CLL亚集，表达对酵母和丝状真菌的主要抗原决定簇β-(1，6)-葡聚糖高度特异的定型BCR。β-(1，6)-葡聚糖的结合依赖于Ig重链和轻链，以及IGHV-CDR3中一个独特的氨基酸。IGHV突变回复到种系构型后，与β-(1，6)-葡聚糖的亲和力降低，表明这些BCR确实是亲和力选择的同源抗原。此外，在β-(1，6)-葡聚糖的刺激下，表达这些定型受体的慢性淋巴细胞性白血病细胞增殖。这项研究建立了一类常见的病原体作为体细胞突变的人类B细胞淋巴瘤的功能配体。
A subset of chronic lymphocytic leukemia with mutated IGHV-genes express BCRs specific for an antigenic determinant of yeast and filamentous fungi, β-(1,6)-glucan. B cell chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is a clonal expansion of CD5+CD19+ B lymphocytes. Two types of CLLs are being distinguished as carrying either unmutated or somatically mutated immunoglobulins (Igs), which are associated with unfavorable and favorable prognoses, respectively. More than 30% of CLLs can be grouped based on their expression of stereotypic B cell receptors (BCRs), strongly suggesting that distinctive antigens are involved in the development of CLL. Unmutated CLLs, carrying Ig heavy chain variable (IGHV) genes in germline configuration, express low-affinity, poly-, and self-reactive BCRs. However, the antigenic specificity of CLLs with mutated IGHV-genes (M-CLL) remained elusive. In this study, we describe a new subset of M-CLL, expressing stereotypic BCRs highly specific for β-(1,6)-glucan, a major antigenic determinant of yeasts and filamentous fungi. β-(1,6)-glucan binding depended on both the stereotypic Ig heavy and light chains, as well as on a distinct amino acid in the IGHV-CDR3. Reversion of IGHV mutations to germline configuration reduced the affinity for β-(1,6)-glucan, indicating that these BCRs are indeed affinity-selected for their cognate antigen. Moreover, CLL cells expressing these stereotypic receptors proliferate in response to β-(1,6)-glucan. This study establishes a class of common pathogens as functional ligands for a subset of somatically mutated human B cell lymphomas.
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影响因子：
3.6
作者：
Gilbert NM;Donlin MJ;Gerik KJ;Specht CA;Djordjevic JT;Wilson CF;Sorrell TC;Lodge JK
通讯作者：
Lodge JK
影响因子：
15.9
作者：
Fais, F;Ghiotto, F;Chiorazzi, N
通讯作者：
Chiorazzi, N
影响因子：
4.8
作者：
Aimanianda, Vishukumar;Clavaud, Cecile;Latge, Jean-Paul
通讯作者：
Latge, Jean-Paul
DOI：
10.1126/science.1221789
发表时间：
2012-06-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iliev ID;Funari VA;Taylor KD;Nguyen Q;Reyes CN;Strom SP;Brown J;Becker CA;Fleshner PR;Dubinsky M;Rotter JI;Wang HL;McGovern DP;Brown GD;Underhill DM
通讯作者：
Underhill DM
DOI：
10.1073/pnas.0811003106
发表时间：
2009-08-04
影响因子：
11.1
作者：
Froehlich-Nowoisky, Janine;Pickersgill, Daniel A.;Poeschl, Ulrich
通讯作者：
Poeschl, Ulrich