Adult B-cell repertoire is biased toward two heavy-chain variable-region genes that rearrange frequently in fetal pre-B cells.
Adult B-cell repertoire is biased toward two heavy-chain variable-region genes that rearrange frequently in fetal pre-B cells.
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成人 B 细胞库偏向于在胎儿前 B 细胞中频繁重排的两个重链可变区基因。
DOI：
10.1073/pnas.84.8.2454
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发表时间：
1987
影响因子：
11.1
通讯作者：
Gearhart,PJ
中科院分区：
文献类型：
--
作者：
Lawler,AM;Lin,PS;Gearhart,PJ
胎儿前B细胞重排重链(VH)的一组非常有限的免疫球蛋白可变基因。为了确定成人B细胞谱系是否也有类似的倾斜，我们首先确定了BALB/c小鼠的前B细胞中重排的基因，然后确定了它们在成年B细胞中的重排频率。在胎儿前B细胞系中，来自7183亚家族的VH81X和来自Q52亚家族的VHOx2两个基因占重排等位基因的75%(P<0.001)。测序分析表明，涉及这两个基因的重排既是有益的，也是非生产性的。根据Southern凝胶分析和RNA测序，这两个VH基因的偏向重排在成年小鼠的B细胞杂交瘤中以22%的频率持续存在。杂交瘤的一个VHOx2重排的序列表明重排是有效的，这表明该基因编码了一种可能参与免疫反应的抗体。这些数据表明，成人B细胞谱系对于单个VH基因的使用不是随机的，它可能是由一些未知的机制塑造的，这些机制导致了个体发育早期某些基因的优先重排。
Fetal pre-B cells rearrange a very restricted set of immunoglobulin variable genes for the heavy chain (VH). To determine whether the adult B-cell repertoire is similarly skewed, we first identified the genes that rearrange in pre-B cells from BALB/c mice and then determined their frequency of rearrangement in adult B cells. In fetal pre-B cell lines, two genes, VH81X from the 7183 subfamily and VHOx2 from the Q52 subfamily, comprise 75% of the rearranged alleles of an estimated 1000 genes (P less than 0.001). Sequencing analyses revealed that rearrangements involving the two genes were both productive and nonproductive. The biased rearrangement of these two VH genes persists in B-cell hybridomas from adult mice at a frequency of 22%, as determined by Southern gel analysis and RNA sequencing. The sequence of one VHOx2 rearrangement from a hybridoma shows that the rearrangement is productive, suggesting that the gene encodes an antibody that could participate in the immune response. The data indicate that the adult B-cell repertoire is not random concerning usage of individual VH genes, and it may be shaped by the unknown mechanisms that cause preferential rearrangement of certain genes early in ontogeny.