Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation
- Author(s)
- Minnich, M; Tagoh, H; Bonelt, P; Axelsson, E; FISCHER, M; Cebolla, B; Tarakhovsky, A; Nutt, SL; Jaritz, M; Busslinger, M;
- Details
- Publication Year 2016-03,Volume 17,Issue #3,Page 331-343
- Journal Title
- Nat Immunol
- Publication Type
- Journal Article
- Abstract
- The transcription factor Blimp-1 is necessary for the generation of plasma cells. Here we studied its functions in plasmablast differentiation by identifying regulated Blimp-1 target genes. Blimp-1 promoted the migration and adhesion of plasmablasts. It directly repressed genes encoding several transcription factors and Aicda (which encodes the cytidine deaminase AID) and thus silenced B cell-specific gene expression, antigen presentation and class-switch recombination in plasmablasts. It directly activated genes, which led to increased expression of the plasma cell regulator IRF4 and proteins involved in immunoglobulin secretion. Blimp-1 induced the transcription of immunoglobulin genes by controlling the 3' enhancers of the loci encoding the immunoglobulin heavy chain (Igh) and kappa-light chain (Igk) and, furthermore, regulated the post-transcriptional expression switch from the membrane-bound form of the immunoglobulin heavy chain to its secreted form by activating Ell2 (which encodes the transcription-elongation factor ELL2). Notably, Blimp-1 recruited chromatin-remodeling and histone-modifying complexes to regulate its target genes. Hence, many essential functions of plasma cells are under the control of Blimp-1.
- Publisher
- NPG
- Research Division(s)
- Molecular Immunology
- PubMed ID
- 26779602
- Publisher's Version
- https://doi.org/10.1038/ni.3349
- NHMRC Grants
- NHMRC/361646, NHMRC/1054925,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-01-29 11:46:06
Last Modified: 2016-05-09 12:29:41