miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling

Hines, Marcus J.; Coffre, Maryaline; Mudianto, Tenny; Panduro, Marisella; Wigton, Eric J.; Tegla, Cosmin; Osorio-Vasquez, Victoria; Kageyama, Robin; Benhamou, David; Perez, Oriana A.; Bajwa, Sofia; McManus, Michael T.; Ansel, K. Mark; Melamed, Doron; Koralov, Sergei B.

doi:10.1016/j.celrep.2020.108436

Cited by 20 publications

(14 citation statements)

References 58 publications

(71 reference statements)

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“…As discussed above, ROS generated by normal metabolism of B cells may sustain such increases by interfering with the catalytic activity of the lipid phosphatase PTEN. The importance of sustained PIP3 in promoting progression toward plasma cell differentiation has been underscored by work in which this process was modulated by enhancing or reducing levels of PI3K products via PTEN regulation or a mutated adapter protein [ 205 – 208 ]. Conversely, signals from Syk [ 209 ], Cbl-mediated degradation [ 210 ], and GSK3 are reported to restrain the progression of GC B cells to plasmablast/plasma cell fates, while sufficient ERK activity appears to reduce the levels of the BACH2 protein, which antagonizes the ability of Blimp1 to drive plasma cell differentiation [ 162 , 211 ].…”

Section: Decisions Decisions—b Cells After Activationmentioning

confidence: 99%

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

et al. 2021

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The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody (Ab) secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against infection. With this backdrop, it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise, persist, and meet the challenge of secreting vast amounts of these glycoproteins. Whereas plasmablasts and plasma cells (PCs) are the primary sources of secreted Abs, the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential fates. At each step, cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for nutrients. Nutrients in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription, translation, and metabolism. This review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab secretion. Salient findings of this group and others, sometimes exhibiting differences, will be summarized with regard to the journey to a distinctive metabolic program in PCs.

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Section: Decisions Decisions—b Cells After Activationmentioning

confidence: 99%

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

et al. 2021

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“…However, further studies are required to evaluate the effect of miR-29c KO on progenitor cell population and immunity of an organism. Interestingly, a recent study showed that ablation of miR-29 in mouse models resulted in loss of mature cells, but not progenitor B cells (Hines et al, 2020). The authors suggested dampening of the phosphatidylinositol 3-kinase (PI3K) signaling and subsequent increase in PTEN expression as the factors responsible for reduced survival and terminal differentiation of mature B cells (Hines et al, 2020).…”

Section: Role Of Mir-29c During B Cell Developmentmentioning

confidence: 99%

“…miR-29 null mice display no change in progenitor or immature B cell populations, suggesting that early B cell development is not affected in these mice. However, a reduction in total B cells in the spleen, owing to increased apoptosis of mature B cells, establishes the role of miR-29 in B cell maturation and proliferation (Hines et al, 2020). The miR-29 family consists of three members, miR-29a, miR-29b, and miR-29c.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development

et al. 2021

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“…Meanwhile, microRNAs have been identified to be crucial for regulating BCR signaling ( 27 ). The miR-29 family had been proven to regulate B-cell terminal differentiation and survival ( 28 ), and miR-29c could regulate Rag1 expression and modulate V(D)J recombination during B cell development ( 29 ). Besides, miR-191 has been identified to modulate B-cell development via targeting transcription factors E2A, Foxp1, and Egr1 ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

Whole-Transcriptome Profiling and circRNA-miRNA-mRNA Regulatory Networks in B-Cell Development

Pan

Ren

et al. 2022

Front. Immunol.

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The generation and differentiation of B lymphocytes (B cells) is a flexible process with many critical regulatory factors. Previous studies indicated that non-coding RNAs play multiple roles in the development of lymphocytes. However, little has been known about the circular RNA (circRNA) profiles and their competing endogenous RNA (ceRNA) networks in B-cell development and differentiation. Here, four B-cell subsets were purified from single-cell suspensions of mouse bone marrow. Then RNA sequencing (RNA-Seq) was used to display expression profiles of circRNAs, miRNAs and mRNAs during B-cell differentiation. 175, 203, 219 and 207 circRNAs were specifically expressed in pro-B cells, pre-B cells, immature B cells and mature B cells, respectively. The circRNA-associated ceRNA networks constructed in two sequential stages of B-cell differentiation revealed the potential mechanism of circRNAs in these processes. This study is the first to explore circRNA profiles and circRNA-miRNA-mRNA networks in different B-cell developmental stages of mouse bone marrow, which contribute to further research on their mechanism in B-cell development and differentiation.

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miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling

Cited by 20 publications

References 58 publications

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development

Whole-Transcriptome Profiling and circRNA-miRNA-mRNA Regulatory Networks in B-Cell Development

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