Tschumper Renee C, Hoelzinger Dominique B, Walters Denise K, Davila Jaime I, Osborne Collin A, Jelinek Diane F
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Immunology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
Noncoding RNA. 2022 Feb 5;8(1):15. doi: 10.3390/ncrna8010015.
The differentiation of B cells into antibody secreting plasma cells (PCs) is governed by a strict regulatory network that results in expression of specific transcriptomes along the activation continuum. In vitro models yielding significant numbers of PCs phenotypically identical to the in vivo state enable investigation of pathways, metabolomes, and non-coding (ncRNAs) not previously identified. The objective of our study was to characterize ncRNA expression during human B cell activation and differentiation. To achieve this, we used an in vitro system and performed RNA-seq on resting and activated B cells and PCs. Characterization of coding gene transcripts, including immunoglobulin (Ig), validated our system and also demonstrated that memory B cells preferentially differentiated into PCs. Importantly, we identified more than 980 ncRNA transcripts that are differentially expressed across the stages of activation and differentiation, some of which are known to target transcription, proliferation, cytoskeletal, autophagy and proteasome pathways. Interestingly, ncRNAs located within Ig loci may be targeting both Ig and non-Ig-related transcripts. ncRNAs associated with B cell malignancies were also identified. Taken together, this system provides a platform to study the role of specific ncRNAs in B cell differentiation and altered expression of those ncRNAs involved in B cell malignancies.
B细胞分化为分泌抗体的浆细胞（PCs）受严格的调控网络支配，该网络导致在激活连续过程中特定转录组的表达。产生大量表型与体内状态相同的PCs的体外模型，能够研究以前未发现的信号通路、代谢组和非编码RNA（ncRNAs）。我们研究的目的是表征人类B细胞激活和分化过程中的ncRNA表达。为实现这一目标，我们使用了一个体外系统，并对静止和激活的B细胞及PCs进行了RNA测序。对包括免疫球蛋白（Ig）在内的编码基因转录本的表征，验证了我们的系统，同时也表明记忆B细胞优先分化为PCs。重要的是，我们鉴定出980多个在激活和分化阶段差异表达的ncRNA转录本，其中一些已知靶向转录、增殖、细胞骨架、自噬和蛋白酶体途径。有趣的是，位于Ig基因座内的ncRNAs可能同时靶向Ig和非Ig相关转录本。还鉴定出了与B细胞恶性肿瘤相关的ncRNAs。综上所述，该系统提供了一个平台，用于研究特定ncRNAs在B细胞分化中的作用以及那些参与B细胞恶性肿瘤的ncRNAs的表达改变。
