Abstract
B-lymphocyte-induced maturation protein-1 (Blimp1), is an evolutionarily conserved transcriptional regulator originally described as a repressor of gene transcription. Blimp1 crucially regulates embryonic development and terminal differentiation in numerous cell lineages, including immune cells. Initial investigations of Blimp1’s role in immunity established its non-redundant role in lymphocytic terminal effector differentiation and function. In B cells, Blimp1 drives plasmablast formation and antibody secretion, whereas in T cells, Blimp1 regulates functional differentiation, including cytokine gene expression. These studies established Blimp1 as an essential transcriptional regulator that promotes efficient and controlled adaptive immunity. Recent studies have also demonstrated important roles for Blimp1 in innate immune cells, specifically myeloid cells, and Blimp1 has been established as an intrinsic regulator of dendritic cell maturation and T cell priming. Emerging studies have determined both conserved and unique functions of Blimp1 in different immune cell subsets, including the unique direct activation of the igh gene transcription in B cells and a conserved antagonism with BCL6 in B cells, T cells, and myeloid cells. Moreover, polymorphisms associated with the gene encoding Blimp1 (PRDM1) have been linked to numerous chronic inflammatory conditions in humans. Blimp1 has been shown to regulate target gene expression by either competing with other transcription factors for binding to the target loci, and/or by recruiting various chromatin-modifying co-factors that promote suppressive chromatin structure, such as histone de-acetylases and methyl-transferases. Further, Blimp1 function has been shown to be essentially dose and context-dependent, which adds to Blimp1’s versatility as a regulator of gene expression. Here, we review Blimp1’s complex roles in immunity and highlight specific gaps in the understanding of the biology of this transcriptional regulator, with a major focus on aspects that could foster the description and understanding of novel pathways regulated by Blimp1 in the immune system.
Highlights
The transcription factor positive regulatory domain 1 (PRDI)-BF1/B-lymphocyte-induced maturation protein-1 (Blimp1), encoded by the polymorphisms associated with the gene encoding Blimp1 (PRDM1) gene, was first described in human sarcoma cell lines as a repressor of the IFN-b gene [1]
BCL6 expression has been shown to be unrestrained in some lymphomas, and it has been proposed that this mediates downregulation of PRDM1 and consequent cancer progression due to a dysregulated Blimp1BCL6 axis [26, 87]
The functions of Blimp1 have been extensively studied in B and T lymphocytes, the underlying molecular mechanisms of action have not been fully elucidated and require further studies
Summary
The transcription factor PRDI-BF1/Blimp, encoded by the PRDM1 gene, was first described in human sarcoma cell lines as a repressor of the IFN-b gene [1]. The same protein, this time in a murine system, was named Blimp (B-lymphocyte-induced maturation protein 1), in work done by Mark Davis and colleagues, which revealed Blimp1’s role in driving functional differentiation and plasmablast formation in murine B lymphoma cell lines [2]. This was followed by the observation that human PRDIBF1 and murine Blimp are highly similar homologs of each other [3]. We will focus on the established roles of Blimp as a transcriptional regulator, both as an activator and a repressor, in immune cell subsets and discuss opportunities to further the understanding of Blimp1’s biology and its role in immune homeostasis and diseases
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