Neuropilin-1 Expression Characterizes T Follicular Helper (Tfh) Cells Activated during B Cell Differentiation in Human Secondary Lymphoid Organs |
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| Authors: | Amédée Renand Pierre Milpied Julien Rossignol Julie Bruneau Fran?ois Lemonnier Michael Dussiot Séverine Coulon Olivier Hermine |
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| Affiliation: | 1. CNRS, UMR 8147, Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.; 2. Service d’Hématologie Adulte, APHP, Hôpital Necker, Paris, France.; 3. Service d’anatomo-pathologie, APHP, Hôpital Necker, Paris, France.; 4. Institut Imagine and Université Sorbonne Paris cité, Paris, France.; Institut National de la Santé et de la Recherche Médicale, France, |
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| 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. |
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