EARLY ONSET OF SOMATIC MUTATION IN IMMUNOGLOBULIN-VH GENES DURING THE PRIMARY IMMUNE-RESPONSE
EARLY ONSET OF SOMATIC MUTATION IN IMMUNOGLOBULIN-VH GENES DURING THE PRIMARY IMMUNE-RESPONSE
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DOI：
10.1084/jem.169.6.2007
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发表时间：
1989-06-01
影响因子：
15.3
通讯作者：
GEARHART, PJ
中科院分区：
文献类型：
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作者：
LEVY, NS;MALIPIERO, UV;GEARHART, PJ
研究了 Ig 可变基因体细胞突变的动态，以确定发生突变的 B 细胞群体。 BALB/cJ小鼠注射PC-KLH，并于5、7和13天后制备脾RNA。 mRNA退火至γ。恒定区引物，用于制备编码 VH 基因的 cDNA 转录本。对对应于来自 VH7183、VH3660 和 VHS107 亚家族的 18 个不同基因的 103 个 cDNA 克隆进行了测序，以鉴定突变。 VH 基因在免疫后第 5 天具有较低水平的突变，并在第 7 天以每代每个核苷酸 10-3 个突变的速度累积更多突变。然而，到第 13 天，每个基因的突变数量没有增加，并且大多数替换编码的替换氨基酸变化聚集在高变区，表明突变过程在第二周不太活跃，并且发生了抗原选择。这些数据与发育调节机制一致，在该机制中，突变在初次免疫反应的第一周内被激活，持续一段有限的时间，之后进行选择以保留有益的突变体。
The dynamics of somatic mutation in Ig variable genes was investigated in order to define a population of B cells undergoing mutation. BALB/cJ mice were injected with PC-KLH, and splenic RNA was prepared 5, 7 and 13 d later. The mRNA was annealed to .gamma. constant region primers to make cDNA transcripts encoding VH genes. 103 CDNA clones corresponding to 18 different genes from the VH7183, VH3660, and VHS107 subfamilies were sequenced to identify mutation. VH genes had a low level of mutation on day 5 after immunization and accumulated more mutation by day 7 at a rate of 10-3 mutations per nucleotide per generation. However, by day 13, the number of mutations per gene did not increase, and most of the substitutions encoded replacement amino acid changes that were clustered in the hypervariable regions, indicating that the mutational process was less active during the second week and that antigen selection had occurred. The data are consistent with a developmentally regulated mechanism in which mutation is activated during the first week of the primary immune response for a limited time period, after which selection acts to preserve the beneficial mutants.