Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow

Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow
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DOI:
10.1182/blood-2003-09-3109
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发表时间:
2004-05-15
期刊:
影响因子:
20.3
通讯作者:
Tangye, SG
Tangye, SG
中科院分区:
医学1区
文献类型:
--
作者:
Ellyard, JI;Avery, DT;Tangye, SG

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浆细胞(PC)代表B细胞分化的最后阶段,并致力于产生免疫球蛋白(IG)。其发育的扰动可导致以PC扩张和高丙种球蛋白血症为特征的人类疾病。免疫球蛋白分泌细胞(ISCs)已被确定在次级淋巴组织和骨髓(BM)。淋巴组织中的大多数ISCs是短命的;相反,迁移到BM的ISCs成为长寿的PC,并继续长时间分泌免疫球蛋白。然而,一个小的人口的长寿PC已被确定在啮齿类动物的脾脏,这表明PC可能会持续存在于次级淋巴组织和脾脏,以及BM,在维持长期的体液免疫中起着重要的作用。出于这些原因,我们检查了人类脾脏中的ISCs,并确定了一个类似于长寿啮齿动物脾脏PC的群体。人类脾脏ISC与BM中长寿的PC具有共同的形态、细胞、分子和功能特征,表明它们对PC谱系的承诺。此外,在脾ISCs中检测到高度突变的免疫球蛋白V区基因,表明它们可能是抗原选择性的,并分泌高亲和力的免疫球蛋白。因此,我们的研究结果表明,脾ISCs在体液免疫中具有重要作用,并可能代表某些B细胞恶液质中受影响的细胞类型。(C)2004年,美国血液学会。
Plasma cells (PCs) represent the final stage of B-cell differentiation and are devoted to the production of immunoglobulin (Ig). Perturbations to their development can result in human disorders characterized by PC expansion and hypergammaglobulinemia. Ig-secreting cells (ISCs) have been identified in secondary lymphoid tissues and bone marrow (BM). Most ISCs in lymphoid tissue are short-lived; in contrast, ISCs that migrate to the BM become long-lived PCs and continue to secrete immunoglobulin for extended periods. However, a small population of long-lived PCs has been identified in rodent spleen, suggesting that PCs may persist in secondary lymphold tissue and that the spleen, as well as the BM, plays an important role in maintaining long-term humoral immunity. For these reasons, we examined ISCs in human spleen and identified a population that appears analogous to long-lived rodent splenic PCs. Human splenic ISCs shared morphologic, cellular, molecular, and functional characteristics with long-lived PCs in BM, demonstrating their commitment to the PC lineage. Furthermore, the detection of highly mutated immunoglobulin V region genes in splenic ISCs suggested they are likely to be antigen-selected and to secrete high-affinity immunoglobulin. Thus, our results suggest that splenic ISCs have an important role in humoral immunity and may represent the affected cell type in some B-cell dyscrasias. (C) 2004 by The American Society of Hematology.