title: Neuropilin-1 expression characterizes T follicular helper (Tfh) cells activated during B cell differentiation in human secondary lymphoid organs.
abstract: 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.
authors.affiliation: CNRS, UMR 8147, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Amédée
authors.initials: A
authors.lastname: Renand
authors.affiliation: CNRS, UMR 8147, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Milpied
authors.affiliation: CNRS, UMR 8147, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France ; Institut Imagine and Université Sorbonne Paris cité, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Rossignol
authors.affiliation: CNRS, UMR 8147, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France ; Service d'anatomo-pathologie, APHP, Hôpital Necker, Paris, France ; Institut Imagine and Université Sorbonne Paris cité, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: Service d'Hématologie Adulte, APHP, Hôpital Necker, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Lemonnier
authors.affiliation: CNRS, UMR 8147, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France ; Institut Imagine and Université Sorbonne Paris cité, Paris, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Dussiot
authors.affiliation: CNRS, UMR 8147, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France ; Institut Imagine and Université Sorbonne Paris cité, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Coulon
authors.affiliation: CNRS, UMR 8147, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France ; Service d'Hématologie Adulte, APHP, Hôpital Necker, Paris, France ; Institut Imagine and Université Sorbonne Paris cité, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology; D039942:Neuropilin-1 / Q000096:biosynthesis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; D039942:Neuropilin-1