Hypermutation, diversity and dissemination of human intestinal lamina propria plasma cells
Hypermutation, diversity and dissemination of human intestinal lamina propria plasma cells
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DOI：
10.1002/eji.1830271131
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发表时间：
1997-11-01
影响因子：
5.4
通讯作者：
Spencer, J
中科院分区：
文献类型：
--
作者：
DunnWalters, DK;Boursier, L;Spencer, J
在这项工作中，我们显微解剖了固有层浆细胞，并使用聚合酶链反应和测序来研究免疫球蛋白（Ig）基因在人肠道中的重排和突变。此外，还设计了针对Ig基因重排的特异性引物，以分析相关B细胞和浆细胞克隆在肠道不同部位的分布。证实了我们早期的工作，肠道IgV(H)基因在老年人（50 - 30岁）的浆细胞中高度突变。IgV(H)基因在11-30岁患者的样本中明显较少突变，在幼儿（< 11岁）的样本中也较少突变。在年龄匹配的标本中，十二指肠和结肠的突变数量相等。利用互补决定区3引物扩增特异性Ig基因重排，也发现了相关的固有层浆细胞沿小肠和结肠存在的证据，尽管这些细胞相当罕见。此外，从离散的固有层区域随机抽样的相关无性系数量分析表明，当地种群是多样化的。这些结果表明，成人肠浆细胞中IgV(H)基因的高度突变是慢性抗原暴露的结果。十二指肠浆细胞与结肠浆细胞一样高度突变，尽管上肠没有本地微生物菌群（肠道浆细胞的刺激物）。它们还表明浆细胞群是多种多样的，可以沿着肠道广泛分布。
In this work we have microdissected lamina propria plasma cells and used polymerase chain reaction and sequencing to investigate immunoglobulin (Ig) gene rearrangements and mutations in human intestine. In addition, specific primers were designed for individual Ig gene rearrangements to analyze the distribution of related B cell and plasma cell clones at different sites along the bowel. Confirming our earlier work, intestinal IgV(H) genes were highly mutated in plasma cells from older individuals (> 30 years). IgV(H) genes were significantly less mutated in samples taken from patients aged 11-30 years, and there were fewer mutations again in samples from young children (< 11 years). In age-matched specimens the number of mutations was equivalent in the duodenum and colon. Using complementarity-determining region 3 primers to amplify specific Ig gene rearrangements, evidence was also found for the existence of related lamina propria plasma cells along the small bowel and colon, although these were quite scarse. In addition, analysis of the numbers of related clones in a random sampling from discrete areas of lamina propria indicates that the local population is diverse. These results suggest that the highly mutated IgV(H) genes in adult intestinal plasma cells are a consequence of chronic antigen exposure with age. Duodenal plasma cells are as highly mutated as colonic plasma cells, despite the fact that the upper bowel has no indigenous microbial flora (the stimulus for intestinal plasma cells). They also show that the plasma cell population is diverse and can be widely disseminated along the bowel.