Lymph Node Stromal Cells Generate Antigen-Specific Regulatory T Cells and Control Autoreactive T and B Cell Responses

Reza Nadafi, Catarina Gago de Graça, Eelco D. Keuning, Jasper J. Koning, Sander de Kivit, Tanja Konijn, Sandrine Henri, Jannie Borst, Rogier M. Reijmers, Lisa G.M. van Baarsen, Reina E. Mebius*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Within lymph nodes (LNs), T follicular helper (TFH) cells help B cells to produce antibodies, which can either be protective or autoreactive. Here, we demonstrate that murine LN stromal cells (LNSCs) suppress the formation of autoreactive TFH cells in an antigen-specific manner, thereby significantly reducing germinal center B cell responses directed against the same self-antigen. Mechanistically, LNSCs express and present self-antigens in major histocompatibility complex (MHC) class II, leading to the conversion of naive CD4+ T cells into T regulatory (TREG) cells in an interleukin-2 (IL-2)-dependent manner. Upon blockade of TREG cells, using neutralizing IL-2 antibodies, autoreactive TFH cells are allowed to develop. We conclude that the continuous presentation of self-antigens by LNSCs is critical to generate antigen-specific TREG cells, thereby repressing the formation of TFH cells and germinal center B cell responses. Our findings uncover the ability of LNSCs to suppress the early activation of autoreactive immune cells and maintain peripheral tolerance.

Original languageEnglish
Pages (from-to)4110-4123.e4
JournalCell Reports
Issue number12
Publication statusPublished - 24 Mar 2020

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