Kuehl W M
Surv Immunol Res. 1983;2(1):52-61. doi: 10.1007/BF02918396.
It has become increasingly apparent that generation of and variation in antigen-combining sites of antibodies occurs sequentially during B-cell development. Allelic and isotypic exclusion mechanisms ensure that a B cell produces antibody molecules having a single kind of combining site. A major reason for evolution of mechanisms which result in asynchronous formation of functional H and L chain genes may be the need for allelic and isotypic exclusion; but this may not be the only advantage of asynchronous formation of H and L chain genes. The evolution of mechanisms causing nonjunctional somatic mutation late in B cell development - only after antigen exposure apparently - may result from the biological advantages of: (1) 'fine tuning' of the combining site; (2) a response to an anti-idiotype regulatory network, or (3) expanded memory.
越来越明显的是，抗体抗原结合位点的产生和变异在B细胞发育过程中是依次发生的。等位基因排斥和同种型排斥机制确保B细胞产生具有单一类型结合位点的抗体分子。导致功能性重链和轻链基因异步形成的机制进化的一个主要原因可能是等位基因排斥和同种型排斥的需要；但这可能不是重链和轻链基因异步形成的唯一优势。在B细胞发育后期——显然仅在抗原暴露后——导致非连接体细胞突变的机制的进化可能源于以下生物学优势：（1）结合位点的“微调”；（2）对抗独特型调节网络的反应，或（3）扩大的记忆。
