Ono Masao, Nose Masato
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
APMIS. 2007 Dec;115(12):1350-6. doi: 10.1111/j.1600-0463.2007.apm_870.xml.x.
Genomic recombination events, including VDJ recombination (VDJR) and class-switch recombination (CSR), are indispensable for the adaptation and progression of the acquired immune system. These processes are completed by orderly, temporal onsets of the gene rearrangements along with B-cell differentiation. The presence of various premature transcripts of immunoglobulin heavy chain (IgH) alleles has been demonstrated during B-cell ontogeny. These include D(H)-J(H) (DJ)-mu, J(H)-mu, and sterile transcripts of C(H). Since these transcripts can be detected during the onset of VDJR and CSR, their presence is believed to reflect a structural change in the genome, favoring VDJR and CSR. This report presents evidence of persistent DJ transcription and onset of CSR on an unproductive IgH allele in peripheral tissues. Nucleotide sequence analysis revealed that these transcripts showed DJ-gamma (Dgamma) configuration and that characteristics of the variable region were essentially the same as those of the DJ-mu transcript previously described. It was noted that the small intestine abundantly expresses Dgamma transcripts with gamma2b and gamma1 isotypes of the IgH constant region. The present findings indicate the onset of CSR preceding V(H) to DJ joining in an unproductive IgH allele of the peripheral B cell and the specificity for the gut-associated condition for B-cell differentiation in the small intestine.
基因组重组事件，包括V(D)J重组（VDJR）和类别转换重组（CSR），对于获得性免疫系统的适应和进展不可或缺。这些过程通过基因重排以及B细胞分化的有序、阶段性起始来完成。在B细胞个体发育过程中已证实存在免疫球蛋白重链（IgH）等位基因的各种早熟转录本。这些包括D(H)-J(H)（DJ）-μ、J(H)-μ以及C(H)的无义转录本。由于这些转录本可在VDJR和CSR起始时检测到，因此认为它们的存在反映了基因组的结构变化，有利于VDJR和CSR。本报告提供了外周组织中无功能IgH等位基因上持续DJ转录和CSR起始的证据。核苷酸序列分析显示这些转录本呈现DJ-γ（Dγ）构型，并且可变区的特征与先前描述的DJ-μ转录本基本相同。值得注意的是，小肠大量表达具有IgH恒定区γ2b和γ1同种型的Dγ转录本。目前的研究结果表明在外周B细胞的无功能IgH等位基因中，CSR起始先于V(H)与DJ连接，并且小肠中B细胞分化具有肠道相关条件的特异性。
