Paper in Cell Reports from Reza Nadafi et al. for research on Lymph node stromal cells, which generate antigen-specific regulatory T cells.
Authors: Reza Nadafi, Eelco D. Keuning, Catarina Gago de Graça, Jasper J. Koning, Sander de Kivit, Tanja Konijn, Sandrine Henri, Jannie Borst, Rogier M. Reijmers, Lisa G. M. van Baarsen, Reina E. Mebius
Abstract
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.