Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice

Ellyard, Julia I.; Chia, Tiongsun; Rodríguez-Pinilla, Socorro-María; Martin, Jeffrey T.; Hu, Xin; Navarro-Gonzalez, Manuel F.; Garcı́a, Juan F.; Delfau‐Larue, Marie‐Hélène; Montes‐Moreno, Santiago; Gaulard, Philippe; Cook, Matthew C.; Walters, Giles; Piris, Miguel Á.; Vinuesa, Carola G.

doi:10.1182/blood-2011-07-365130

Cited by 39 publications

(49 citation statements)

References 49 publications

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“…Mice carrying heterozygous null-mutations of the tg roquin (RC3H1) gene develop accumulations of T FH cells with abnormal expression of ICOS and eventually develop a MTCL [17]. Although these proliferations share many clinical, histological, and phenotypic features with human AITL, the infiltrated lymph nodes (LN) lack the characteristic expanded FDC network and hyperplastic germinal centers (GC) found in human AITL.…”

Section: Genetically Engineered Mouse Models For Mtclmentioning

confidence: 99%

Models for mature T-cell lymphomas—A critical appraisal of experimental systems and their contribution to current T-cell tumorigenic concepts

Warner¹,

Crispatzu²,

Al-Ghaili³

et al. 2013

Critical Reviews in Oncology/Hematology

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Section: Genetically Engineered Mouse Models For Mtclmentioning

confidence: 99%

Models for mature T-cell lymphomas—A critical appraisal of experimental systems and their contribution to current T-cell tumorigenic concepts

Warner¹,

Crispatzu²,

Al-Ghaili³

et al. 2013

Critical Reviews in Oncology/Hematology

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“…130). In mice, heterozygosity for a Roquin-1 mutation that causes T cell–autonomous T FH expansion also leads to an AITL-like disease 131 . These mutations have not been found in humans, but mutations in TET2, IDH2, DNMT3A and RHOA are commonly found in AITL 132–134 .…”

Section: Tfh Cells In Cancermentioning

confidence: 99%

Pathophysiology of T follicular helper cells in humans and mice

Ueno¹,

2015

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Follicular helper T cells (TFH cells) compose a heterogeneous subset of CD4+ T cells that induce the differentiation of B cells into plasma cells and memory cells. They are found within and in proximity to germinal centers in secondary lymphoid organs, and their memory compartment also circulates in the blood. Our knowledge on the biology of TFH cells has increased significantly during the past decade, largely as a result of mouse studies. However, recent studies on human TFH cells isolated from lymphoid organ and blood samples and recent observations on the developmental mechanism of human TFH cells have revealed both similarities and differences between human and mouse TFH cells. Here we present the similarities and differences between mouse and human lymphoid organ–resident TFH cells and discuss the role of TFH cells in response to vaccines and in disease pathogenesis.

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“…AITL is a peripheral T cell lymphoma that derives from Tfh cells [34,35,45]. Our study of five cases of AITL revealed that Nrp1 expression in malignant PD-1 + T cells is not systematic.…”

Section: Discussionmentioning

confidence: 85%

Neuropilin-1 Expression Characterizes T Follicular Helper (Tfh) Cells Activated during B Cell Differentiation in Human Secondary Lymphoid Organs

et al. 2013

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T follicular helper (Tfh) cells play an essential role in the development of antigen-specific B cell immunity. Tfh cells regulate the differentiation and survival of activated B cells outside and inside germinal centers (GC) of secondary lymphoid organs. They act through cognate contacts with antigen-presenting B cells, but there is no current marker to specifically identify those Tfh cells which productively interact with B cells. Here we show that neuropilin 1 (Nrp1), a cell surface receptor, is selectively expressed by a subset of Tfh cells in human secondary lymphoid organs. Nrp1 expression on Tfh cells correlates with B cell differentiation in vivo and in vitro, is transient, and can be induced upon co-culture with autologous memory B cells in a cell contact-dependent manner. Comparative analysis of ex vivo Nrp1+ and Nrp1- Tfh cells reveals gene expression modulation during activation. Finally, Nrp1 is expressed by malignant Tfh-like cells in a severe case of angioimmunoblastic T-cell lymphoma (AITL) associated with elevated terminal B cell differentiation. Thus, Nrp1 is a specific marker of Tfh cells cognate activation in humans, which may prove useful as a prognostic factor and a therapeutic target in neoplastic diseases associated with Tfh cells activity.

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Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice

Cited by 39 publications

References 49 publications

Models for mature T-cell lymphomas—A critical appraisal of experimental systems and their contribution to current T-cell tumorigenic concepts

Models for mature T-cell lymphomas—A critical appraisal of experimental systems and their contribution to current T-cell tumorigenic concepts

Pathophysiology of T follicular helper cells in humans and mice

Neuropilin-1 Expression Characterizes T Follicular Helper (Tfh) Cells Activated during B Cell Differentiation in Human Secondary Lymphoid Organs

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