Dataset Information

The B Cell Activation-Induced miR-183 Cluster Plays a Minimal Role in Canonical Primary Humoral Responses.

ABSTRACT: Although primary humoral responses are vital to durable immunity, fine-tuning is critical to preventing catastrophes such as autoimmunity, chronic inflammation, and lymphomagenesis. MicroRNA (miRNA)-mediated regulation is particularly well suited for fine-tuning roles in physiology. Expression of clustered paralogous miR-182, miR-96, and miR-183 (collectively, 183c) is robustly induced upon B cell activation, entry into the germinal center, and plasmablast differentiation. 183cGT/GT mice lacking 183c miRNA expression exhibit largely normal primary humoral responses, encompassing class switch recombination, affinity maturation, and germinal center reaction, as well as plasmablast differentiation. Our rigorous analysis included ex vivo class switch recombination and plasmablast differentiation models as well as in vivo immunization with thymus-dependent and thymus-independent Ags. Our work sways the debate concerning the role of miR-182 in plasmablast differentiation, strongly suggesting that 183c miRNAs are dispensable. In the process, we present a valuable framework for systematic evaluation of primary humoral responses. Finally, our work bolsters the notion of robustness in miRNA:target interaction networks and advocates a paradigm shift in miRNA studies.

SUBMITTER: Pucella JN

PROVIDER: S-EPMC6986270 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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The B Cell Activation-Induced miR-183 Cluster Plays a Minimal Role in Canonical Primary Humoral Responses.

Pucella Joseph N JN Cols Montserrat M Yen Wei-Feng WF Xu Shunbin S Chaudhuri Jayanta J

Journal of immunology (Baltimore, Md. : 1950) 20190125 5

Although primary humoral responses are vital to durable immunity, fine-tuning is critical to preventing catastrophes such as autoimmunity, chronic inflammation, and lymphomagenesis. MicroRNA (miRNA)-mediated regulation is particularly well suited for fine-tuning roles in physiology. Expression of clustered paralogous miR-182, miR-96, and miR-183 (collectively, 183c) is robustly induced upon B cell activation, entry into the germinal center, and plasmablast differentiation. 183c<sup>GT/GT</sup> m ...[more]

PMID: 30683701

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Project description:Epstein-Barr virus (EBV) is an oncogenic human herpesvirus involved in the pathogenesis of Burkitt's lymphoma (BL) and various other lymphoproliferative disorders. In BL, EBV protein expression is restricted to EBV nuclear antigen 1 (EBNA1), but small noncoding RNAs such as EBV-encoded small RNAs (EBERs) and microRNAs (miRNAs) can also be detected. miRNAs play major roles in crucial processes such as proliferation, differentiation, and cell death. It has recently become clear that alterations in the expression profile of miRNAs contribute to the pathogenesis of a number of malignancies. During latent infection, EBV expresses 25 viral pre-miRNAs and modulates the expression of specific cellular miRNAs, such as miR-155 and miR-146, which potentially play a role in oncogenesis. Here, we established the small-RNA expression profiles of three BL cell lines. Using large-scale sequencing coupled to Northern blotting and real-time reverse transcription-PCR (RT-PCR) analysis validation, we demonstrated the differential expression of some cellular and viral miRNAs. High-level expression of the miR-183-96-182 cluster and EBV miR-BamHI A rightward transcript (miR-BART) cluster was significantly associated with EBV type I latency. This expression was not affected by viral reactivation since transforming growth factor ?1 (TGF-?1) stimulation did not significantly change the miRNA profiles. However, using several approaches, including de novo infection with a mutant virus, we present evidence that the expression of latent membrane protein 1 (LMP-1) triggered downregulation of the expression of the miR-183-96-182 cluster. We further show that this effect involves the Akt signaling pathway.In addition to expressing their own miRNAs, herpesviruses also impact the expression levels of cellular miRNAs. This regulation can be either positive or negative and usually results in the perturbation of pathways to create a cellular environment that is more "virus-friendly." For example, EBV induces the expression of miR-155, a well-characterized oncomiR, which leads to increased cell proliferation and decreased cell death. Here, we show that EBV-encoded LMP-1 is also involved in the downregulation of a cluster of three miRNAs, miR-183, -96, and -182, which are known to be also repressed in several cancers. We therefore identify yet another potential player in EBV-induced oncogenesis.

Dataset Information

The B Cell Activation-Induced miR-183 Cluster Plays a Minimal Role in Canonical Primary Humoral Responses.

Publications

The B Cell Activation-Induced miR-183 Cluster Plays a Minimal Role in Canonical Primary Humoral Responses.

Similar Datasets

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