Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow.
Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow.
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DOI：
10.1016/j.immuni.2015.06.016
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发表时间：
2015-07-21
期刊：
影响因子：
32.4
通讯作者：
Lee FE
中科院分区：
文献类型：
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作者：
Halliley JL;Tipton CM;Liesveld J;Rosenberg AF;Darce J;Gregoretti IV;Popova L;Kaminiski D;Fucile CF;Albizua I;Kyu S;Chiang KY;Bradley KT;Burack R;Slifka M;Hammarlund E;Wu H;Zhao L;Walsh EE;Falsey AR;Randall TD;Cheung WC;Sanz I;Lee FE
针对病毒感染的抗体反应通过长寿命浆细胞 (LLPC) 维持数十年。然而，LLPCs 尚未在人类身上得到表征。在这里，我们使用 CD19、CD38 和 CD138 来鉴定人骨髓 (BM) 中的四个 PC 亚群。我们发现 CD19−CD38hiCD138+ 子集在形态上是不同的、差异表达的 PC 相关基因，并且只包含对受试者 40 多年未接触过的病毒抗原具有特异性的 PC。麻疹和腮腺炎特异性循环抗体的蛋白质序列由 BM 中的 CD19−CD38hiCD138+ PC 编码。最后，我们发现 CD19−CD38hiCD138+ PC 具有独特的 RNA 转录组特征和人免疫球蛋白重链 (VH) 库，与其他 BM PC 亚群相对分离，并且可能代表 B 细胞反应的抗原暴露的“历史记录”。因此，我们的研究定义了人类 LLPC，并提供了一种终生维持血清中抗病毒抗体的机制。
Antibody responses to viral infections are sustained for decades by long-lived plasma cells (LLPCs). However, LLPCs have yet to be characterized in humans. Here we used CD19, CD38, and CD138 to identify four PC subsets in human bone marrow (BM). We found that the CD19−CD38hiCD138+ subset was morphologically distinct, differentially expressed PC-associated genes and exclusively contained PCs specific for viral antigens to which the subjects had not been exposed for over 40 years. Protein sequences of measles- and mumps-specific circulating antibodies were encoded for by CD19−CD38hiCD138+ PCs in the BM. Finally, we found that CD19−CD38hiCD138+ PCs had a distinct RNA transcriptome signature and human immunoglobulin heavy chain (VH) repertoire that was relatively uncoupled from other BM PC subsets and likely represents the B cell response’s “historical record” of antigenic exposure. Thus, our studies define human LLPCs and provide a mechanism for the life-long maintenance of anti-viral antibodies in the serum.