microRNA-155 Regulates the Generation of Immunoglobulin Class-Switched Plasma Cells

By E. Vigorito, K. L. Perks, Cei Abreu-Goodger, S. Bunting, Z. Xiang, S. Kohlhaas, P. Das, E. Miska, Antony Rodríguez, A. Bradley and 6 more. Immunity, 2007

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Summary MicroRNA-155 (miR-155) is expressed by cells of the immune system following activation and has been shown to be required for antibody production following vaccination with attenuated Salmonella. Here we show the intrinsic requirement for miR-155 in B cell responses to thymus-dependent and independent antigens. B cells lacking miR-155 generated reduced extra-follicular and germinal center responses and failed to produce high affinity IgG1 antibodies. Gene expression profiling of activated B cells indicated that miR-155 regulates an array of genes with diverse function-many of which are predicted targets of miR-155. The transcription factor Pu.1 is validated as a direct target of miR155 mediated inhibition. When Pu.1 is over-expressed in wild type B cells fewer IgG1 cells are produced, indicating that loss of Pu.1 regulation is a contributing factor to the miR-155 deficient phenotype. Our results implicate post-transcriptional regulation of gene expression for establishing the terminal differentiation program of B cells.

Subfields: Animal Science and Zoology, Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6bbc77a62f3a311876494458db8ebb8955044f5c

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Citations in the corpus

microRNAs and the immune response (2009, background): “Current Opinion in Pharmacology 2009, 9:514–520 the involvement of miR-155 in B-cell production of high affinity IgG1 antibodies, the development of B-cell memory and the production of cytokines such as TNFa and lymphotoxin-a/b [28 ,36].”
MicroRNA control in the immune system: basic principles. (2009, background): “In the former case, miR-155 downregulates AID, an essential enzyme for class switch recombination (CSR), and the transcription factor Pu.1, which counteracts the differentiation of class-switched cells.”
Physiological and pathological roles for microRNAs in the immune system (2010, background): “miR-155-deficient B cells have defective antibody class switching and differentiation into plasma cells, resulting in an impaired humoral response to T cell-dependent antigenic stimulatio”
Inositol phosphatase SHIP1 is a primary target of miR-155 (2009, background): “1 (22), AID (47, 48), SOCS1 (49), and now SHIP1, suggest that individual targets likely make significant contributions to miR-155 function in a context-dependent manner.”
MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells (2009, background): “1 and to influence B cell development (15, 25).”
An overview of microRNAs (2015, background): “miRNAs have been linked to the function of many hematopoietic lineages including neutrophils, lymphocytes, erythrocytes, megakaryocytes, an hematopoetic stem cells [17, 150-161].”
Role of microRNAs in vascular diseases, inflammation, and angiogenesis. (2008, background): “In addition, miR-155 is required for B and T lymphocyte and dendritic cell function.(69,70) Mechanistically, the transcription factor Pu.”
MicroRNAs in development and disease. (2011, background): “1, which reduces IgG1 switching and is a target of miR-155 (636).”
Akt1 controls macrophage response to LPS by regulating microRNAs (2009, background): “…miR-155 is upregulated in response to LPS (O’Connell et al., 2007; Tili et al., 2007), promoting the expression of TNF-a and destabilization of PU.1 (Vigorito et al., 2007), a key mediator of monocyte and macrophage differentiation and TLR4 transcription (Roger et al., 2005; Tsatsanis et al.,…”
MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development (2010, background): “Beyond its role in mediating inflammatory T cell development as identified in our current study, previous reports have clearly shown that miR-155 is important for production of antigen-specific IgGs (Rodriguez et al., 2007; Thai et al., 2007; Vigorito et al., 2007).”