microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells.
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.
Vigorito
Elena
E
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, CB22 3AT, UK. elena.vigorito@bbsrc.ac.uk
Perks
Kerry L
KL
Abreu-Goodger
Cei
C
Bunting
Sam
S
Xiang
Zou
Z
Kohlhaas
Susan
S
Das
Partha P
PP
Miska
Eric A
EA
Rodriguez
Antony
A
Bradley
Allan
A
Smith
Kenneth G C
KG
Rada
Cristina
C
Enright
Anton J
AJ
Toellner
Kai-Michael
KM
Maclennan
Ian C M
IC
Turner
Martin
M
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000502:physiology; D007109:Immunity; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D010950:Plasma Cells / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D027041:Somatic Hypermutation, Immunoglobulin; D015534:Trans-Activators / Q000502:physiology; D000099232:Proto-Oncogene Protein Spi-1
D007074:Immunoglobulin G; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1