Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase.
Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase.
复制标题
免疫球蛋白基因的体细胞超突变不依赖于布卢姆综合征 DNA 解旋酶。
DOI：
10.1046/j.1365-2249.1998.00575.x
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发表时间：
1998
影响因子：
4.6
通讯作者：
Green,NS
中科院分区：
文献类型：
--
作者：
Sack,SZ;Liu,Y;German,J;Green,NS
免疫球蛋白基因体细胞突变通过在抗原结合位点引入多个点突变导致抗体亲和力成熟。尚未发现参与这一过程的基因。布卢姆综合征 (BS) 是一种具有突变表型的染色体断裂性疾病。大多数受影响的个体表现出病因不明的免疫缺陷。这种疾病的基因 BLM 最近被鉴定为 DNA 解旋酶。如果该基因在免疫球蛋白突变中发挥作用，那么患有 BS 的人可能缺乏正常突变的抗体。由于种系、非突变的免疫球蛋白基因通常产生低亲和力抗体，解旋酶活性受损可能表现为 BS 中发现的免疫缺陷。因此，我们询问 BLM 是否特异性参与免疫球蛋白超突变。对从 BS 个体获得的未分选的少量血液样本中分析免疫球蛋白可变 (V) 区的序列，并与种系序列进行比较。 BS V区突变呈正态分布，表明BS缺陷与体细胞突变机制无关。这些数据强烈反对 BLM 参与这一过程。识别免疫球蛋白突变相关基因的遗传学方法需要对 DNA 修复和免疫缺陷个体进行进一步研究。
Immunoglobulin gene somatic mutation leads to antibody affinity maturation through the introduction of multiple point mutations in the antigen binding site. No genes have as yet been identified that participate in this process. Bloom's syndrome (BS) is a chromosomal breakage disorder with a mutator phenotype. Most affected individuals exhibit an immunodeficiency of undetermined aetiology. The gene for this disorder,BLM, has recently been identified as a DNA helicase. If this gene were to play a role in immunoglobulin mutation, then people with BS may lack normally mutated antibodies. Since germ‐line, non‐mutated immunoglobulin genes generally produce low affinity antibodies, impaired helicase activity might be manifested as the immunodeficiency found in BS. Therefore, we asked whetherBLMis specifically involved in immunoglobulin hypermutation. Sequences of immunoglobulin variable (V) regions were analysed from small unsorted blood samples obtained from BS individuals and compared with germ‐line sequences. BS V regions displayed the normal distribution of mutations, indicating that the defect in BS is not related to the mechanism of somatic mutation. These data strongly argue againstBLMbeing involved in this process. The genetic approach to identifying the genes involved in immunoglobulin mutation will require further studies of DNA repair‐ and immunodeficient individuals.