ORGANIZATION, STRUCTURE, AND ASSEMBLY OF IMMUNOGLOBULIN HEAVY-CHAIN DIVERSITY DNA SEGMENTS

ORGANIZATION, STRUCTURE, AND ASSEMBLY OF IMMUNOGLOBULIN HEAVY-CHAIN DIVERSITY DNA SEGMENTS
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DOI:
10.1084/jem.155.1.201
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发表时间:
1982-01-01
影响因子:
15.3
通讯作者:
TONEGAWA, S
TONEGAWA, S
中科院分区:
医学1区
文献类型:
--
作者:
KUROSAWA, Y;TONEGAWA, S

文献摘要

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对编码小鼠IGH链基因多样性(D)区的8个不同DNA片段进行鉴定、克隆和测序。与先前表征的2D片段一样,所有8D片段的侧翼都是由12个碱基对(bp)间隔区隔开的特征性七聚体和九聚体。这10个D片段(以及几个鉴定但尚未测序的D片段)可以根据序列同源性的程度分为3个家族。SP2家族由9个高度同源的D片段组成,它们都是17-bp长,并聚集在染色体区域中。60 kb。FL 16家族由多达4个D片段组成,其中2个被定位在SP2-D簇的5“端区域。2个FL 16 D片段长23和17 bp。第三个是Q52家族,是一个10 bp长的DQ 52的单成员家族,位于JH簇5“的700 bp处。大多数H链基因的D区序列显然是通过各种体细胞机制(包括多个D片段的连接)从这些生殖系D片段中产生的。提出了一种不违反12/23-bp间隔区规则的D-D连接的具体模型。
Eight different DNA segments encoding the diversity (D) regions of mouse IGH-chain genes were identified, cloned and sequenced. Like the 2 D segments previously characterized, all 8 D segments are flanked by characteristic heptamers and nonamers separated by 12 base pair (bp) spacers. These 10 D segments (and several more D segments identified but not yet sequenced) can be classified into 3 families based on the extent of sequence homology. The SP2 family consists of 9 highly homologous D segments that are all 17-bp long and clustered in a chromosomal region of .apprx. 60 kb. The FL 16 family consists of up to 4 D segments, 2 of which were mapped in the 5'' end region of the SP2-D cluster. The 2 FL16D segments are 23 and 17 bp long. The 3rd, the Q52 family, is a single-member family of the 10-bp-long DQ52, located 700 bp 5'' to the JH cluster. The D-region sequences of the majority of H chain genes evidently arise from these germline D segments by various somatic mechanisms, including joining of multiple D segments. A specific model of D-D joining that does not violate the 12/23-bp spacer rule is presented.