Transcriptional Repressor Blimp-1 Promotes CD8+ T Cell Terminal Differentiation and Represses the Acquisition of Central Memory T Cell Properties

Rutishauser, Rachel L.; Martins, Gislâine A.; Kalachikov, Sergey; Chandele, Anmol; Parish, Ian A.; Meffre, Eric; Jacob, Joshy; Calame, Kathryn; Kaech, Susan M.

doi:10.1016/j.immuni.2009.05.014

Cited by 511 publications

(673 citation statements)

References 63 publications

Supporting

Mentioning

623

Contrasting

Unclassified

Order By: Relevance

“…1A), matching our previous observations with anti-TT ASCs (11). These Blimp-1 GFP/+ cells expressed high levels of CD138, the PC marker, for the largest part were not Blimp-1 GFP/+ CD8 + T cells (25,26) and displayed the characteristic morphology of PCs (Supplemental Fig. 1B).…”

Section: Distribution and Preferential Proximity Of Pcs In The Bm Comsupporting

confidence: 88%

Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche

Belnoue

Tougne²,

Rochat³

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

According to commonly held concepts, plasma cell (PC) longevity in bone marrow (BM) depends upon their access to survival niches. These are thought to exist in nursery cell types, which support PCs by secreting PC survival factors. To better define PC survival niches and their functioning, we adoptively transferred traceable Blimp-1-GFP PCs into recipient mice lacking a proliferation-inducing ligand (APRIL), IL-6, or macrophage migration inhibitory factor. Transferred BMPCs were preferentially associated with Ly-6Chigh monocytes (normalized colocalization index: 9.84), eosinophils (4.29), and megakaryocytes (2.12). Although APRIL was essential for BMPC survival, PC recruitment into the proximity of nursery cells was unimpaired in APRIL-deficient mice, questioning the concept that the same factors account for attraction/retention of PCs as for their local survival. Rather, the order of colocalization with BMPCs (monocytes > eosinophils > megakaryocytes) reflected these cells’ relative expression of CXCR4, VLA-4, and LFA-1, the homing and adhesion molecules that direct/retain PCs in the BM. This suggests a scenario wherein the cellular composition of the BMPC niche is defined by a common pattern of attraction/retention on CXCL12-abundant reticular docking cells. Thereby, PCs are directed to associate in a functional BM niche with hematopoietic CXCR4+VLA-4+LFA-1+ nursery cells, which provide PC survival factors.

show abstract

Section: Distribution and Preferential Proximity Of Pcs In The Bm Comsupporting

confidence: 88%

Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche

Belnoue

Tougne²,

Rochat³

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Of particular interest is a DMR in the Blimp1 (Prdm 1) locus that remains methylated in the MP subset. This is consistent with prior reports showing that MP cells have reduced Blimp1 expression relative to the TE subset and that deletion of Blimp 1 increases the number of effector cells with memory potential 13 . We also detected differential methylation of Runx2 and Runx3 further suggesting that MP and TE fates are coupled to epigenetic programming of transcriptional regulators.…”

supporting

confidence: 93%

Effector CD8 T cells dedifferentiate into long-lived memory cells

Youngblood

Hale

Kissick

et al. 2017

Nature

381

359

View full text Add to dashboard Cite

Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These resting memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogen, but also have many properties in common with naïve cells, including the ability to migrate to lymph nodes and spleen, and their pluri-potency. Thus, memory cells embody features of both naïve and effector cells, fueling a long-standing debate centered on whether memory T cells develop from effector cells or directly from naïve cells1–4. To better define the developmental path of memory CD8 T cells we investigated changes in DNA methylation programming at naïve and effector genes in virus specific CD8 T cells during acute LCMV infection of mice. Methylation profiling of effector CD8 T cell subsets at day 4 and 8 after infection showed that, rather than retaining a naïve epigenetic state, the subset of cells that gives rise to memory cells acquired de novo DNA methylation programs at naïve-associated genes and became demethylated at loci of classically defined effector molecules. Conditional deletion of the de novo methyltransferase, Dnmt3a, at an early stage of effector differentiation strikingly reduced methylation of naïve-associated genes and resulted in faster re-expression of these naïve genes, accelerating memory cell development. Longitudinal phenotypic and epigenetic characterization of virus-specific memory-precursor CD8 T cells transferred into antigen-free mice revealed that their differentiation into memory cells was coupled to cell-division independent erasure of de novo methylation programs and re-expression of naïve-associated genes. These data provide evidence that epigenetic repression of naïve-associated genes in effector CD8 T cells can be reversed in cells that develop into long-lived memory CD8 T cells supporting a differentiation model where memory T cells arise from a subset of fate-permissive effector T cells.

show abstract

“…Prdm1-induced maturation of lymphocytes is correlated with the ability of Prdm1 to repress numbers of genes critical for mature B cell identity and cellular proliferation [5,[8][9][10][11][12][13]. Prdm1 is also needed for the activation of T cells [14][15][16][17][18], the differentiation of myeloid lineage [19] and the maturation of nature killer (NK) cells [20].…”

Section: Introductionmentioning

confidence: 99%

Identification and expression profiles of prdm1 in medaka Oryzias latipes

et al. 2013

View full text Add to dashboard Cite

Mouse Prdm1, also known as Blimp1, plays important roles in maturation and survival of lymphoid cells, as well as in organogenesis of muscle, limb, sensor organs and primordial germ cells. The homologues of mouse prdm1 have been identified in a diverse of animals including zebrafish and fugu. Here, we report the identification and expression profiles of two homologues of prdm1, namely prdm1a and prdm1b in medaka, Oryzias latipes. The transcripts of prdm1a and prdm1b were detectable in all the tissues including immune organs such as gill, spleen, kidney, liver and intestine that we have checked on. The transcripts of prdm1a could be detected in the embryonic shield at mid-gastrula stage and later in the somite, eye, otic vesicle, branchial arches, fin, intestine and cloaca during embryogenesis using in situ hybridization. Moreover, the expression of prdm1a in the liver of both medaka and zebrafish could be up-regulated by the immune stimuli including lipopolysaccharide, polyI:C and the grass carp reovirus, similarly to the up-regulation of IL1B. These results indicate that Prdm1a may play important roles in embryogenesis and also in immune response in fish.

show abstract

Transcriptional Repressor Blimp-1 Promotes CD8+ T Cell Terminal Differentiation and Represses the Acquisition of Central Memory T Cell Properties

Cited by 511 publications

References 63 publications

Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche

Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche

Effector CD8 T cells dedifferentiate into long-lived memory cells

Identification and expression profiles of prdm1 in medaka Oryzias latipes

Contact Info

Product

Resources

About