Abstract：
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.
摘要：
在广泛的文献中描述了淋巴细胞对移植相关病理的贡献，包括同种异体移植排斥和移植物抗宿主病，以T细胞为中心的研究已经超过了对B细胞的研究。大多数B细胞相关报告描述了调节和抗体产生功能，很少关注抗原呈递能力的潜在作用。使用体外人混合淋巴细胞反应（MLRs）模拟同种异体刺激，我们使用转录分析分析了应答者B细胞，流式细胞术和显微镜。我们观察到激活的应答者B细胞亚群的出现，表型与移植物抗宿主病或同种异体移植物排斥反应的个体相似。该群体具有显著增加的FcRL5(Fc受体样5)和与HLAI类抗原呈递相关的分子的表达。与这种表型一致，这些细胞表现出辐射细胞碎片和葡聚糖大分子的内化增加。MLR反应者中这个亚群的比例也与激活的出现相关，细胞毒性CD8+T细胞。具有相似特征的B细胞在健康个体的未刺激血液中很少见，但在分解的人脾细胞中很容易识别，并且在同种异体刺激后两种情况下都增加。该亚群的出现和功能的进一步表征可能潜在地有助于鉴定与遏制移植相关病理相关的新型生物标志物和靶向疗法。
