Single-cell transcriptomics of peripheral blood reveals a novel B-cell subset in renal allograft recipients with accommodation

Kidney transplantation is a preeminent treatment for end-stage renal disease . The application of immunosuppressants is needed for kidney recipients to avoid allograft rejection but increase the risk of infection, and balance between rejection and infection is an important in clinical to reach the immune accommodation. Here, we use single-cell RNA sequencing to fully assess the immune status of peripheral mononuclear cells in kidney recipients. and compared the differences between kidney recipients and healthy people to describe the characteristics of the immune accommodation of kidney recipients. We found a novel B cell subset (CD19+IGKC+IGLC3lowTCL1A-CD127+) of renal transplant recipients with accommodation was significantly lower than that of healthy people and verified by flow cytometry. which may have potential regulatory potential. Furthermore, we found that IL32 may increase the expression of CD19+IGKC+IGLC3lowTCL1A-CD127+ Bcells. In summary, we found that the CD19+IGKC+IGLC3lowTCL1A-CD127+B subgroup with immunomodulatory potential is inhibited in kidney recipients with accommodation state, and IL-32 has therapeutic potential for this. Overall design: Sc-RNA-seq for PBMC from kidney recipients, patient with end stage renal disease and healthy control. 3 sample: title; source name; tissue; age; gender KTx; kidney recipient; blood; 32; male HC; healthy control; blood; 30; male ESRD; end-stage renal disease; blood; 35; male

肾脏移植是终末期肾病（end-stage renal disease, ESRD）的首选治疗方案。肾移植受者需使用免疫抑制剂以避免同种异体移植排斥反应，但此类药物会增加感染风险，因此在排斥反应与感染之间寻求平衡，是临床实现免疫耐受（immune accommodation）的核心目标。
本研究采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）全面评估肾移植受者外周血单个核细胞（peripheral mononuclear cells, PBMC）的免疫状态，并对比肾移植受者与健康人群的免疫特征，以阐明肾移植受者的免疫耐受特性。
研究发现，处于免疫耐受状态的肾移植受者体内存在一类新型B细胞亚群（CD19+IGKC+IGLC3lowTCL1A-CD127+），其比例显著低于健康人群，该结果经流式细胞术（flow cytometry）验证，且该亚群可能具备潜在的免疫调节功能。
进一步研究显示，白介素32（IL32）可上调CD19+IGKC+IGLC3lowTCL1A-CD127+ B细胞的表达水平。
综上，本研究证实，具有免疫调节潜力的CD19+IGKC+IGLC3lowTCL1A-CD127+ B细胞亚群在免疫耐受状态的肾移植受者中受到抑制，而IL-32对此具备潜在治疗价值。
实验整体设计：对肾移植受者、终末期肾病患者及健康对照的外周血单个核细胞进行单细胞RNA测序。共纳入3例样本，具体信息如下：
1. KTx：肾移植受者，样本来源为血液，年龄32岁，男性
2. HC：健康对照，样本来源为血液，年龄30岁，男性
3. ESRD：终末期肾病患者，样本来源为血液，年龄35岁，男性