Myeloid Cells Limit Production of Antibody-Secreting Cells after Immunization in the Lymph Node
Myeloid Cells Limit Production of Antibody-Secreting Cells after Immunization in the Lymph Node
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DOI：
10.4049/jimmunol.1300977
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发表时间：
2014-02-01
影响因子：
4.4
通讯作者：
Dustin, Michael L.
中科院分区：
文献类型：
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作者：
Fooksman, David R.;Nussenzweig, Michel C.;Dustin, Michael L.
抗体分泌细胞（ASC）的扩增和存活是优化疫苗和控制自身免疫的重要过程。髓索的微环境被定位以控制这些关键过程。以前，我们成像和特点的ASC分化和迁移的活体显微镜在淋巴结（LN）转移和激活B细胞表达黄色荧光蛋白，只有在ASC室。在这项研究中，我们观察到，黄色荧光蛋白（+）ASCs在髓索迁移沿着骨髓单核细胞，并停止与他们接触。使用在Lysmd 1-cre阳性细胞中表达的人白喉受体系统（白喉毒素受体[DTR]）急性消融骨髓细胞使ASC和Ab产生增加2倍。基于Ki-67染色，ASC数量的增加与细胞增殖相关，而不是细胞凋亡减少或LN出口的变化。使用DTR介导的靶向Ccr 2表达骨髓细胞的消融也产生了ASC的增加。相比之下，无论是用Ab耗尽Gr-1阳性细胞还是使用cd 11 c-DTR消融细胞都不会导致ASC的任何变化。IL-6细胞因子信号传导可以增强ASC产生，并且已经涉及通过骨髓细胞抑制狼疮小鼠模型中的ASC。使用混合骨髓嵌合体，我们观察到IL-6增强ASC的产生，但IL-6的产生并不是骨髓细胞抑制LN中ASC所必需的。这些髓样细胞在LN中对ASC的抑制提供了一种新的调节机制，其对调节Ab反应具有意义。
Ab-secreting cell (ASC) expansion and survival are important processes in optimizing vaccines and controlling autoimmunity. The microenvironment of the medullary cords is positioned to control these key processes. Previously, we imaged and characterized ASC differentiation and migration by intravital microscopy in the lymph node (LN) by transferring and activating B cells expressing yellow fluorescent protein only in the ASC compartment. In this study, we observed that yellow fluorescent protein(+) ASCs in the medullary cords migrated along myelomonocytic cells and arrested in contact with them. Acute ablation of myeloid cells using the human diphtheria receptor system (diphtheria toxin receptor [DTR]) expressed in Lysmd1-cre-positive cells increased ASC and Ab production by 2-fold. Increases in ASC numbers were associated with cell proliferation based on Ki-67 staining, rather than reduced apoptosis, or changes in egress from the LN. Using DTR-mediated ablation targeted to Ccr2-expressing myeloid cells also generated increases in ASCs. In contrast, neither the depletion of Gr-1-positive cells with an Ab nor the ablation of cells using a cd11c-DTR resulted in any change in ASCs. IL-6 cytokine signaling can enhance ASC production and has been implicated in dampening ASCs in lupus mouse models through myeloid cells. Using mixed bone marrow chimeras, we observed that IL-6 enhances ASC production, but IL-6 production was not required by myeloid cells to dampen ASCs in the LN. Inhibition of ASCs by these myeloid cells in the LN provides a new regulatory mechanism with implications for tuning Ab responses.