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单词 somatic recombination
释义
somatic recombination

Biology
  • A mechanism for generating diversity of antibodies in B cells and of receptors in T cells (see T-cell receptor). The variable regions of an antibody’s light (VL) and heavy (VH) chains, which determine the molecule’s binding properties for antigen, are encoded by genes that are assembled from either two (in the case of VL) or three (for VH) gene segments. Both VL and VH chains are joined to an additional constant region (CL and CH, respectively), encoded by a further set of genes. The mature VL gene is made up of a V gene segment and a J(or joining) gene segment. For example, the human λ‎ light chain genetic locus spans 1050 kbp on chromosome 22 and comprises several clusters of gene segments encoding constant, variable, and joining regions of the light chain. There are thought to be about 29–33 functional V gene segments, 4–5 functional J gene segments, and 4–5 constant gene segments. So there are potentially of the order 30 × 5 = 150 different combinations of V and J gene segments, which means that 150 different mature VL genes can be made. Adding to this the 230 possible combinations for the second type of light chain (κ‎ light chains, encoded by a gene cluster on chromosome 2) makes 380 different light chains. Heavy chain genes contain a third gene segment, called a diversity (or DH) gene segment, and possible combinations of the VH, DH, and JH segments found at the heavy chain locus on chromosome 14 total roughly 6000. Therefore, altogether there are theoretically 1.9 × 106 (i.e. 320 × 6000) different combinations of the several different antibody regions due to somatic recombination. This is one way in which B cells generate their vast repertoire of antibodies. The recombination mechanism, called V(D)J recombination, is a multistep enzymatic process requiring the products of two genes that are expressed only in developing lymphocytes, namely the recombination-activating genes RAG1 and RAG2. Diversity of T-cell receptors is generated by a similar mechanism involving the rearrangement of gene segments encoding variable regions of the α‎ and β‎ chains. Further diversity is generated by additional mechanisms, namely D-J recombination, which causes variation in amino acid sequence at the D-J junction of the heavy chain, and somatic hypermutation. All these mechanisms together account for potentially something of the order of 1013 different antibodies—sufficient to match the great diversity of potential antigens.


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