Luby T M, Schrader C E, Stavnezer J, Selsing E
Department of Pathology, Program in Immunology, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
J Exp Med. 2001 Jan 15;193(2):159-68. doi: 10.1084/jem.193.2.159.
Class switch DNA recombinations change the constant (C) region of the antibody heavy (H) chain expressed by a B cell and thereby change the antibody effector function. Unusual tandemly repeated sequence elements located upstream of H chain gene exons have long been thought to be important in the targeting and/or mechanism of the switch recombination process. We have deleted the entire switch tandem repeat element (S(mu)) from the murine (mu) H chain gene. We find that the S(mu) tandem repeats are not required for class switching in the mouse immunoglobulin H-chain locus, although the efficiency of switching is clearly reduced. Our data demonstrate that sequences outside of the S(mu) tandem repeats must be capable of directing the class switch mechanism. The maintenance of the highly repeated S(mu) element during evolution appears to reflect selection for a highly efficient switching process rather than selection for a required sequence element.
类别转换DNA重组可改变B细胞表达的抗体重链(H链)的恒定(C)区,从而改变抗体效应功能。长期以来,人们一直认为位于H链基因外显子上游的异常串联重复序列元件在转换重组过程的靶向和/或机制中很重要。我们已从小鼠μH链基因中删除了整个转换串联重复元件(S(μ))。我们发现,尽管转换效率明显降低,但S(μ)串联重复对于小鼠免疫球蛋白H链基因座中的类别转换并非必需。我们的数据表明,S(μ)串联重复序列之外的序列必定能够指导类别转换机制。在进化过程中高度重复的S(μ)元件得以保留,这似乎反映了对高效转换过程的选择,而非对必需序列元件的选择。