Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612-7344, USA.
Department of Bioengineering, University of Illinois Colleges of Engineering and Medicine, Chicago, IL 60612-7344, USA.
Cell Rep. 2021 Nov 23;37(8):110059. doi: 10.1016/j.celrep.2021.110059.
Class-switch recombination (CSR) involves replacement of the Cμ constant region with another downstream C region. CSR is initiated by activation-induced cytidine deaminase (AID)-mediated DNA breaks that are targeted to transcriptionally active switch (S) regions. S region promoters (Prs) direct synapsis by associating with the Eμ and 3'Eα enhancers that jointly anchor a chromatin loop. We report that asymmetric loop extrusion allows 3'Eα to track along the locus and form Pr-Pr-E interactions that mediate CSR between downstream S regions, followed by switching to donor Sμ. This alternative pathway bypasses sequential switching and creates immunoglobulin (Ig)E B cells in the absence of IgG1 expression. Based on the analysis of diagnostic CSR products in B cell subsets, we identify a BCR-negative cell intermediate that is pivotal to efficient CSR.
类别转换重组（CSR）涉及用另一个下游 C 区替换 Cμ 恒定区。CSR 是由激活诱导的胞嘧啶脱氨酶（AID）介导的 DNA 断裂启动的，这些断裂靶向转录活跃的开关（S）区。S 区启动子（Prs）通过与 Eμ 和 3'Eα 增强子结合来指导联会，共同锚定染色质环。我们报告说，不对称的环挤出允许 3'Eα 沿着基因座追踪，并形成 Pr-Pr-E 相互作用，介导下游 S 区之间的 CSR，然后切换到供体 Sμ。这种替代途径绕过了顺序转换，并在没有 IgG1 表达的情况下产生了免疫球蛋白（Ig）E B 细胞。基于对 B 细胞亚群中诊断性 CSR 产物的分析，我们确定了一个 BCR 阴性细胞中间产物，它是有效 CSR 的关键。
