Valor Luis M, Rodríguez-Bayona Beatriz, Ramos-Amaya Ana B, Brieva José A, Campos-Caro Antonio
Unidad de Investigación, Hospital Universitario Puerta del Mar and Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz (INiBICA), Cádiz, Spain.
PLoS One. 2017 Aug 17;12(8):e0183264. doi: 10.1371/journal.pone.0183264. eCollection 2017.
Plasma cells (PC) represent the heterogeneous final stage of the B cells (BC) differentiation process. To characterize the transition of BC into PC, transcriptomes from human naïve BC were compared to those of three functionally-different subsets of human in vivo-generated PC: i) tonsil PC, mainly consisting of early PC; ii) PC released to the blood after a potent booster-immunization (mostly cycling plasmablasts); and, iii) bone marrow CD138+ PC that represent highly mature PC and include the long-lived PC compartment. This transcriptional transition involves subsets of genes related to key processes for PC maturation: the already known protein processing, apoptosis and homeostasis, and of new discovery including histones, macromolecule assembly, zinc-finger transcription factors and neuromodulation. This human PC signature is partially reproduced in vitro and is conserved in mouse. Moreover, the present study identifies genes that define PC subtypes (e.g., proliferation-associated genes for circulating PC and transcriptional-related genes for tonsil and bone marrow PC) and proposes some putative transcriptional regulators of the human PC signatures (e.g., OCT/POU, XBP1/CREB, E2F, among others). Finally, we also identified a restricted imbalance of the present PC transcriptional program in monoclonal gammopathies that correlated with PC malignancy.
浆细胞（PC）代表B细胞（BC）分化过程的异质性终末阶段。为了表征BC向PC的转变，将人类初始BC的转录组与人类体内产生的PC的三个功能不同亚群的转录组进行了比较：i）扁桃体PC，主要由早期PC组成；ii）强效加强免疫后释放到血液中的PC（大多为循环浆母细胞）；以及iii）骨髓CD138 + PC，代表高度成熟的PC，包括长寿PC区室。这种转录转变涉及与PC成熟关键过程相关的基因子集：已知的蛋白质加工、凋亡和稳态，以及新发现的包括组蛋白、大分子组装、锌指转录因子和神经调节的基因。这种人类PC特征在体外部分重现，并且在小鼠中保守。此外，本研究鉴定了定义PC亚型的基因（例如，循环PC的增殖相关基因以及扁桃体和骨髓PC的转录相关基因），并提出了一些人类PC特征的假定转录调节因子（例如，OCT/POU、XBP1/CREB、E2F等）。最后，我们还在单克隆丙种球蛋白病中鉴定出当前PC转录程序的有限失衡，其与PC恶性肿瘤相关。
