Ongoing Ig gene hypermutation in salivary gland mucosa-associated lymphoid tissue-type lymphomas
Ongoing Ig gene hypermutation in salivary gland mucosa-associated lymphoid tissue-type lymphomas
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DOI：
10.1182/blood.v89.9.3335
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发表时间：
1997-05-01
期刊：
影响因子：
20.3
通讯作者：
Swerdlow, SH
中科院分区：
文献类型：
--
作者：
Bahler, DW;Miklos, JA;Swerdlow, SH
唾液腺粘膜相关淋巴组织（MALT）型淋巴瘤是通常与舍格伦综合征相关的典型惰性B细胞肿瘤。为了更好地定义起源细胞并评估抗原受体刺激是否在肿瘤生长中起作用，将IG重链和轻链可变基因对5例涎腺MALT淋巴瘤表达的VH和VL基因进行了克隆和测序，与已知的种系序列比较表明，其中3个淋巴瘤VH基因来源于51 p1，VH 1家族的成员，而另外两个使用来自VH 3家族的不同VH基因片段，22-2B和HG 19。所有五个VL基因都属于VkIII家族，其中三个来自Humkv 325，另外两个来自Vg和Humkv 328基因。在所有淋巴瘤VH和VL基因中存在相对于所提出的生殖系基因的许多点突变。此外，来自每种淋巴瘤的VH和VL基因显示出指示正在进行的体细胞超突变的克隆内序列异质性。因为IG基因超突变的过程被认为发生在B细胞发育的生殖中心阶段，这些发现提示MALT淋巴瘤细胞起源可能是生殖中心B细胞。针对导致氨基酸替换的突变的选择表明，IG刺激可能对淋巴瘤生长是重要的。抗原受体刺激可能参与唾液腺MALT淋巴瘤的生长的可能性进一步由所注意到的VH和VL基因片段的限制使用提出。(C)1997年，美国血液学会。
Salivary gland mucosa-associated lymphoid tissue (MALT) type lymphomas are typically indolent B-cell neoplasms that are often associated with Sjogren's syndrome, To better define the cell of origin and evaluate whether antigen receptor stimulation may be playing a role in tumor growth, the Ig heavy and light chain variable genes (VH and VL) expressed by five salivary gland MALT lymphomas were cloned and sequenced, Comparison to known germline sequences indicated that three of the lymphoma VH genes were derived from 51p1, a member of the VH1 family, while the other two used different VH gene segments from the VH3 family, 22-2B and HG19. All five of the VL genes belonged to the VkIII family, with three derived from Humkv325 and the other two from the Vg and Humkv328 genes. Numerous point mutations relative to the proposed germline genes were present in all of the lymphoma VH and VL genes, In addition, the VH and VL genes from each lymphoma showed intraclonal sequence heterogeneity indicative of ongoing somatic hypermutation, Because the process of Ig gene hypermutation is thought to occur at the germinal center stage of B cell development, these findings suggest the MALT lymphoma cell of origin may be a germinal center B cell. Selection against mutations that result in replacement of amino acids suggested that Ig stimulation may be important for lymphoma growth, The possibility that antigen receptor stimulation may be involved in the growth of salivary gland MALT lymphomas is further suggested by the noted restricted use of VH and VL gene segments. (C) 1997 by The American Society of Hematology.