Department of Microbiology, University of Chicago, Chicago, IL, United States.
Department of Immunobiology, Yale University, New Haven, CT, United States.
Front Immunol. 2024 Mar 5;15:1345467. doi: 10.3389/fimmu.2024.1345467. eCollection 2024.
The vast diversity of mammalian adaptive antigen receptors allows for robust and efficient immune responses against a wide number of pathogens. The antigen receptor repertoire is built during the recombination of B and T cell receptor (BCR, TCR) loci and hypermutation of BCR loci. V(D)J recombination rearranges these antigen receptor loci, which are organized as an array of separate V, (D), and J gene segments. Transcription activation at the recombining locus leads to changes in the local three-dimensional architecture, which subsequently contributes to which gene segments are utilized for recombination. The endogenous retrovirus (ERV) mouse mammary tumor provirus 8 () resides on mouse chromosome 6 interposed within the large array of light chain kappa V gene segments. As ERVs contribute to changes in genomic architecture by driving high levels of transcription of neighboring genes, it was suggested that could influence the BCR repertoire. We generated -deficient mice to determine if the ERV influences V(D)J recombination to test this possibility. We find that does not influence the BCR repertoire.
哺乳动物适应性抗原受体的巨大多样性允许针对大量病原体产生强大而有效的免疫反应。抗原受体库是在 B 和 T 细胞受体 (BCR、TCR) 基因座的重组和 BCR 基因座的超突变过程中构建的。V(D)J 重组重新排列这些抗原受体基因座,这些基因座被组织成一系列单独的 V、(D)和 J 基因片段。在重组基因座的转录激活导致局部三维结构发生变化,随后影响用于重组的基因片段。内源性逆转录病毒 (ERV) 小鼠乳腺肿瘤病毒 8()位于小鼠染色体 6 上,位于大型轻链 κ V 基因片段阵列之间。由于 ERV 通过驱动邻近基因的高水平转录来导致基因组结构发生变化,因此有人提出可以影响 BCR 库。我们生成了 - 缺陷小鼠,以确定 ERV 是否通过影响 V(D)J 重组来测试这种可能性。我们发现不影响 BCR 库。