Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors
Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors
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DOI：
10.1172/jci3009
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发表时间：
1998-10-15
影响因子：
15.9
通讯作者：
Chiorazzi, N
中科院分区：
文献类型：
--
作者：
Fais, F;Ghiotto, F;Chiorazzi, N
为了更好地了解 B 型慢性淋巴细胞白血病 (B-CLL) 细胞达到的分化阶段，并深入了解抗原刺激在这些细胞的发育和多样化中的潜在作用，我们分析了 83 个 B-CLL 细胞（64 个 IgM(+) 和 19 个非 IgM(+)）表达的重排 V-H 基因。我们的结果证实并扩展了 B-CLL 细胞中某些 V-H、D 和 J(H) 基因使用存在偏差的观察结果。此外，他们还表明，与50%的IgM(+) B-CLL细胞相似的V-H基因和与75%的非IgM(+) B-CLL细胞相似的V-H基因可以表现出体细胞突变。突变的存在根据 B-CLL 细胞表达的 V-H 家族而变化（V(H)3 表达者比 V(H)1 和 V(H)4 表达者显示更多突变）。此外，突变程度可能相当大，类似于 32% 的 IgM(+) 病例和类似于 68% 的非 IgM(+) 病例，与最相似的种系基因相差 > 5%。大约 20% 的突变 V-H 基因以与抗原选择一致的模式显示替代突变。然而，CDR3 特征（D 和 J(H) 基因使用和关联以及 HCDR3 长度、组成和电荷）表明，对不同 B 细胞受体 (BCR) 的选择发生在更多的 B-CLL 细胞中。根据这些数据，我们提出了三个原型 BCR，代表我们研究中最常遇到的 V-H 基因。这些数据表明许多 B-CLL 细胞先前已被刺激，将它们置于“经验丰富”或“记忆”CD5(+) B 细胞亚群中。
To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged V-H genes expressed by 83 B-CLL cells (64 IgM(+) and 19 non-IgM(+)). Our results confirm and extend the observations of a bias in the use of certain V-H, D, and J(H) genes among B-CLL cells. In addition, they indicate that the V-H genes of similar to 50% of the IgM(+) B-CLL cells and similar to 75% Of the non-IgM(+) B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the V-H family expressed by the B-CLL cell (V(H)3 expressers displaying more mutation than V(H)1 and V(H)4 expressers). In addition, the extent of mutation can be sizeable with similar to 32% of the IgM(+) cases and similar to 68% of the non-IgM(+) cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated V-H genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and J(H) gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the V-H genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.