B-Cell chronic lymphocytic leukemia, a clonal disease of B lymphocytes with receptors that vary in specificity for (auto)antigens
B-Cell chronic lymphocytic leukemia, a clonal disease of B lymphocytes with receptors that vary in specificity for (auto)antigens
复制标题
DOI：
10.1196/annals.1358.002
复制
发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Albesiano, E
中科院分区：
文献类型：
--
作者：
Chiorazzi, N;Hatzi, K;Albesiano, E
B细胞慢性淋巴细胞白血病（B-CLL）是一种不治之症，在老年白人中相对常见。可使用临床分期参数以及分子特征[编码白血病B细胞抗原受体（BCR）的重排V（H）DJ（H）片段中存在或不存在IgV（H）突变]将患有这种白血病的患者分为预后类别。此外，属于不同预后类别的患者的BCR的推导氨基酸结构在这些组内不同程度地共享。本文综述了编码B-CLL患者BCR的基因的分子特征，这些特征与已知特异性的抗体相比较。这些比较表明，许多病例的BCR类似于自身抗体，在某些情况下，类似于微生物抗原的抗体。抗原结合分析证实了这些印象，也表明，多反应性似乎区分病例与更好的临床结果不同。自身反应性和多反应性的持续存在有些令人惊讶，因为IgV DNA序列分析表明，许多变成白血病的B细胞经历了一种或另一种形式的受体编辑。因此，B-CLL似乎是一种B细胞克隆的疾病，这些B细胞克隆经历了各种类型的受体重构，但仍保留了不适当的抗原结合特性。
B-Cell chronic lymphocytic leukemia (B-CLL) is an incurable disease that is relatively common among aging Caucasians. Patients with this leukemia can be divided into prognostic categories using clinical staging parameters, as well as molecular features [presence or absence of IgV(H) mutations in rearranged V(H)DJ(H) segments that code for the leukemic B cell's receptor for antigen (BCR)]. In addition, the deduced amino acid structure of the BCRs from patients that fall into different prognostic categories is shared, to varying degrees, within these groups. In this paper, the molecular features of the genes that code for the BCRs of B-CLL patients are reviewed, and these are comapred to antibodies of known specificity. These comparisons suggest that the BCRs of many cases resemble autoantibodies, and in some cases, antibodies to microbial antigens. Antigen-binding analyses confirm these impressions, and also indicate that polyreactivity appears to distinguish cases with worse clinical outcomes differ from those with better outcomes. The persistence of autoreactivity and polyreactivity is somewhat surprising, because IgV DNA sequence analyses suggest that many of the B cells that become leukemic have undergone one form or another of receptor editing. Thus, B-CLL appears to be a disease of B-cell clones that have undergone various types of receptor reconfiguration and yet retain inappropriate antigen-binding properties.