Department of Orthopedics, Beijing Second Hospital, Beijing 100031, China.
Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, Xian 710038, China.
J Immunol Res. 2019 Feb 18;2019:9561350. doi: 10.1155/2019/9561350. eCollection 2019.
Neutrophils have recently been proposed as cells with high functional plasticity and are involved in the pathogenesis of infections, malignancy, and autoimmune diseases. However, less is known about the role of neutrophil in humoral response. In this study, we examined the importance of neutrophils and the neutrophil-derived DAMP protein, MRP14, in antibody production. Splenic neutrophils and MRP14 that are present in the splenic peri-MZ region have a close contact with MZ B cells and promote their differentiation into plasma cells. Using neutrophil-depleting mice and an MRP14-blocking compound, we showed that the presence of neutrophil and MRP14 is required for class switch, plasma cell maintenance, and antibody production in the spleen. We found that MRP14 could also be produced by neutrophils in the bone marrow and support the maintenance of bone marrow plasma cells. MRP14 binding could enhance the effect of the BAFF signal and protect primary multiple myeloma cells from doxorubicin-induced apoptosis. Our data demonstrate the effects of neutrophils on neighboring B cells and plasma cells, which provides new insights into the connection between neutrophil and humoral responses.
中性粒细胞最近被认为是具有高功能可塑性的细胞，参与感染、恶性肿瘤和自身免疫性疾病的发病机制。然而，关于中性粒细胞在体液反应中的作用知之甚少。在这项研究中，我们研究了中性粒细胞和中性粒细胞衍生的 DAM 蛋白 MRP14 在抗体产生中的重要性。脾脏中的中性粒细胞和存在于脾脏边缘区的 MRP14 与边缘区 B 细胞密切接触，并促进其分化为浆细胞。使用中性粒细胞耗竭小鼠和 MRP14 阻断化合物，我们表明中性粒细胞和 MRP14 的存在是类转换、浆细胞维持和脾脏中抗体产生所必需的。我们发现 MRP14 也可以由骨髓中的中性粒细胞产生，并支持骨髓浆细胞的维持。MRP14 结合可以增强 BAFF 信号的作用，并保护原发性多发性骨髓瘤细胞免受阿霉素诱导的凋亡。我们的数据表明了中性粒细胞对邻近 B 细胞和浆细胞的影响，这为中性粒细胞和体液反应之间的联系提供了新的见解。
