异体刺激导致人类 B 细胞群的出现,其 HLA I 类抗原呈递相关分子和免疫球蛋白受体 FcRL5 的表达量增加。

IF 8.9 2区 医学 Q1 SURGERY American Journal of Transplantation Pub Date : 2024-11-01 DOI:10.1016/j.ajt.2024.06.014
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引用次数: 0

摘要

在描述淋巴细胞对移植相关病症(包括异体移植物排斥反应和移植物抗宿主疾病)的作用的大量文献中,以 T 细胞为重点的研究超过了对 B 细胞的研究。大多数与 B 细胞相关的报告都描述了 B 细胞的调节和抗体生成功能,而较少关注其抗原提呈能力的潜在作用。我们使用体外人类混合淋巴细胞反应(MLRs)来模拟异源刺激,并使用转录分析、流式细胞仪和显微镜分析了应答B细胞。我们观察到出现了一种活化的应答B细胞亚群,其表型与患有移植物抗宿主疾病或异体移植物排斥反应的个体所描述的亚群相似。该亚群的 FcRL5(类 Fc 受体 5)和 HLA I 类抗原呈递相关分子的表达明显增加。与这一表型相一致的是,这些细胞对辐照细胞碎片和葡聚糖大分子的内化也有所增加。该亚群在 MLR 反应者中的比例也与活化的细胞毒性 CD8+ T 细胞的出现相关。类似特征的 B 细胞在健康人的未刺激血液中并不常见,但在分解的人脾细胞中却很容易识别,并且在异体刺激时都会增加。对这一亚群的出现和功能的进一步描述可能有助于确定新型生物标志物和靶向治疗方法,从而遏制与移植相关的病理现象。
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Allostimulation leads to emergence of a human B cell population with increased expression of HLA class I antigen presentation–associated molecules and the immunoglobulin receptor FcRL5
In the extensive literature characterizing lymphocyte contributions to transplant-related pathologies including allograft rejection and graft-versus-host disease, T cell–focused investigation has outpaced investigation of B cells. Most B cell–related reports describe regulatory and antibody-producing functions, with less focus on the potential role of antigen-presenting capacity. Using in vitro human mixed lymphocyte reactions (MLRs) to model allostimulation, we analyzed responder B cells using transcriptional analysis, flow cytometry, and microscopy. We observed emergence of an activated responder B cell subpopulation phenotypically similar to that described in individuals with graft-versus-host disease or allograft rejection. This population had markedly increased expression of FcRL5 (Fc receptor like 5) and molecules associated with human leukocyte antigen class I antigen presentation. Consistent with this phenotype, these cells demonstrated increased internalization of irradiated cell debris and dextran macromolecules. The proportion of this subpopulation within MLR responders also correlated with emergence of activated, cytotoxic CD8+ T cells. B cells of similar profile were quite infrequent in unstimulated blood from healthy individuals but readily identifiable in disaggregated human splenocytes and increased in both cases upon allostimulation. Further characterization of the emergence and function of this subpopulation could potentially contribute to identification of novel biomarkers and targeted therapeutics relevant to curbing transplant-related pathology.
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来源期刊
CiteScore
18.70
自引率
4.50%
发文量
346
审稿时长
26 days
期刊介绍: The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide. The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.
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