免疫球蛋白的基因重排

<font> <span> </span> <span>免疫球蛋白是具有抗原决定簇结合特异性的各种球蛋白分子的总称。多样性是免疫球蛋白的重要特性。自然界的抗原种类极多，每种抗原还有不同的抗原决定簇，因此具有多种特异性的免疫球蛋白分子的种类也必定是极其众多的，可以有几百万种。可是，脊椎动物<a href="https://www.biomart.cn/supply/1001011605.htm">基因组</a>内所有的基因总共不过几万个左右。因此，决不可能有那么多的免疫球蛋白基因去编码每一种特定的免疫球蛋白分子。研究证明，这是通过基因重排来实现免疫球蛋白的多样性。在胚胎细胞中，</span> <span>V</span> <span>、</span> <span>J</span> <span>、</span> <span>(D)</span> <span>和</span> <span>C</span> <span>基因是分散排列的，在</span> <span>B</span> <span>细胞发育成熟过程中，基因组中组成免疫球蛋白分子的各个基因开始发生重排，</span> <span>V</span> <span>区基因发生</span> <span>y</span> <span>—</span> <span>J</span> <span>或</span> <span>y</span> <span>—</span> <span>D</span> <span>—</span> <span>J</span> <span>重排，与</span> <span>C</span> <span>基因连接，转录产生</span> <span>mRNA</span> <span>。随机重排的结果可以产生</span> <span>108</span> <span>—</span> <span>10l0</span> <span>种免疫球蛋白分子。</span> </font>

<font><span> 1</span> <span>．轻链基因的重排</span> </font>

<font><span> </span> <span>κ基因可通过</span> <span>V</span> <span>κ。区基因的缺失、倒位而与相隔一定距离的一个</span> <span>J</span> <span>κ。基因相连接</span> <b><span>(</span> <span>图</span> <span>6</span> <span>—</span> <span>28)</span> </b> <span>。κ链的</span> <span>V</span> <span>区基因可随机地同任何一个</span> <span>J</span> <span>κ基因连接。重排后的</span> <span>V</span> <span>κ</span> <span>J</span> <span>κ再与</span> <span>C</span> <span>κ连接生成完整的κ链</span> <span>DNA</span> <span>，其中的内含子在转录后剪接形成</span> <span>mRNA</span> <span>。因为</span> <span>V</span> <span>κ与</span> <span>J</span> <span>κ的重排是随机的，以</span> <span>300</span> <span>个</span> <span>V</span> <span>κ基因同</span> <span>4</span> <span>个</span> <span>J</span> <span>κ基因计算，重排的组合可达</span> <span>1 200</span> <span>种。由于</span> <span>V</span> <span>κ和</span> <span>J</span> <span>κ的连接不够精确，将造成更多的排列组合，可能使多样性增加</span> <span>10</span> <span>倍。</span> <span> </span> </font>

<font><span> V</span> <span>κ和</span> <span>J</span> <span>κ，基因的连接不是随机的，而是严格地按照</span> <span>L</span> <span>λ</span> <span>1 V</span> <span>λ</span> <span>1 J</span> <span>λ</span> <span>1 C</span> <span>λ</span> <span>1</span> <span>，</span> <span>L</span> <span>λ</span> <span>1 V</span> <span>λ</span> <span>1J</span> <span>λ</span> <span>3</span> <span>，</span> <span>C</span> <span>λ</span> <span>3</span> <span>以及</span> <span>L</span> <span>λ</span> <span>2 V</span> <span>λ</span> <span>2 J</span> <span>λ</span> <span>2 C</span> <span>λ</span> <span>2</span> <span>的组合进行连接的，所以入轻链的组合数远低于κ链。</span> </font>

<font><span> 2</span> <span>，重链基因的重排</span> <span> </span> <span>重链基因是通过两次重排形成的。第一次基因重排是</span> <span>D</span> <span>基因与</span> <span>J</span> _{<span>H</span>} <span>基因的重排连接，得到</span> <span>DJ</span> _{<span>H</span>} <span>基因片段；第二次基因重排是</span> <span>V</span> _{<span>H</span>} <span>基因与</span> <span>DJ</span> _{<span>H</span>} <span>基因片段的重排和连接，得到</span> <span>V</span> _{<span>H</span>} <span>DJ</span> _{<span>H</span>} <span>片段</span> <b><span>(</span> <span>图</span> <span>6</span> <span>—</span> <span>29)</span> </b> <span>。两次重排后的基因片段中有一个内含子，在</span> <span>L</span> <span>基因的上游为启动子。</span> <span>H</span> <span>链基因重排过程中，</span> <span>V</span> _{<span>H</span>} <span>、</span> <span>D</span> <span>、</span> <span>J</span> _{<span>H</span>} <span>之间的组合是随机的。</span> <span>H</span> <span>链基因不同的组合数可达</span> <span>500(V)</span> <span>×</span> <span>20(D)</span> <span>×</span> <span>4(J)=4</span> <span>×</span> <span>10</span> ^{<span>4</span>} <span>。如果考虑到其他各种因素如连接的不精确性等，估计</span> <span>H</span> <span>链的多样性可达</span> <span>4X10</span> ^{<span>7</span>} <span>。</span> <span>H</span> <span>链和</span> <span>L</span> <span>链可能的组合数预计可达</span> <span>10</span> ^{<span>11</span>} <span>以上。小鼠每天生成的淋巴细胞为</span> <span>10</span> ^{<span>8</span>} <span>个，可见动物一生中还不可能使全部可能产生的基因组合得到表达。</span> </font>

(责任编辑：大汉昆仑王)