Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA
Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA
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DOI：
10.1182/blood-2008-06-162024
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发表时间：
2008-12-15
期刊：
影响因子：
20.3
通讯作者：
Chiorazzi, Nicholas
中科院分区：
文献类型：
--
作者：
Chu, Charles C.;Catera, Rosa;Chiorazzi, Nicholas
一大群无关慢性淋巴细胞白血病（CLL）患者的白血病B淋巴细胞表达由IGHV 1 -69、IGHD 3 -16和IGHJ 3编码的未突变重链免疫球蛋白可变（V）区，其重链和轻链互补决定区3序列几乎相同。这些患者随机产生具有相同抗体V区的CLL克隆的可能性是非常不可能的，并且表明通过共同抗原的选择。来自该定型子集的单克隆抗体（mAb）强烈结合HEp-2细胞中的细胞质结构。因此，HEp-2细胞提取物与重组定型亚群特异性CLL mAb进行免疫沉淀，揭示了约225 kDa的主要蛋白条带，通过质谱法鉴定为非肌肉肌球蛋白重链IIA（MYHIIA）。通过Western印迹和与抗MYHIIA抗体的免疫荧光共定位证实了定型mAb与MYHIIA的反应性。改变MYHIIA量和细胞质定位的处理导致与这些mAb结合的相应变化。MYHIIA在经历应激或凋亡的细胞表面上的出现表明CLL mAb通常可以结合由于这些事件而暴露的分子。CLL mAb与MYHIIA的结合可促进这些白血病细胞的发育、存活和扩增。（血。2008; 112：5122-5129）
Leukemic B lymphocytes of a large group of unrelated chronic lymphocytic leukemia (CLL) patients express an unmutated heavy chain immunoglobulin variable (V) region encoded by IGHV1-69, IGHD3-16, and IGHJ3 with nearly identical heavy and light chain complementarity-determining region 3 sequences. The likelihood that these patients developed CLL clones with identical antibody V regions randomly is highly improbable and suggests selection by a common antigen. Monoclonal antibodies (mAbs) from this stereotypic subset strongly bind cytoplasmic structures in HEp-2 cells. Therefore, HEp-2 cell extracts were immunoprecipitated with recombinant stereotypic subset-specific CLL mAbs, revealing a major protein band at approximately 225 kDa that was identified by mass spectrometry as nonmuscle myosin heavy chain IIA (MYHIIA). Reactivity of the stereotypic mAbs with MYHIIA was confirmed by Western blot and immunofluorescence colocalization with anti-MYHIIA antibody. Treatments that alter MYHIIA amounts and cytoplasmic localization resulted in a corresponding change in binding to these mAbs. The appearance of MYHIIA on the surface of cells undergoing stress or apoptosis suggests that CLL mAb may generally bind molecules exposed as a consequence of these events. Binding of CLL mAb to MYHIIA could promote the development, survival, and expansion of these leukemic cells. (Blood. 2008; 112: 5122-5129)