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

Elena Vigorito, Kerry L. Perks, Cei Abreu-Goodger, Sam Bunting, Zou Xiang, Susan Kohlhaas, Partha P. Das, Eric A. Miska, Antony Rodriguez, Allan Bradley, Kenneth G.C. Smith, Cristina Rada, Anton J. Enright, Kai Michael Toellner, Ian C.M. MacLennan, Martin Turner

Research output: Contribution to journalArticleResearchpeer-review

573 Citations (Scopus)

Abstract

microRNA-155 (miR-155) is expressed by cells of the immune system after activation and has been shown to be required for antibody production after 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 extrafollicular 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 overexpressed 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.

Original languageEnglish
Pages (from-to)847-859
Number of pages13
JournalImmunity
Volume27
Issue number6
DOIs
Publication statusPublished - 21 Dec 2007
Externally publishedYes

Keywords

  • MOLIMMUNO
  • RNA

Cite this