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Peripheral tolerance in lymph nodes (LNs) is maintained by fibroblastic reticular cells (FRCs) via self\u2010antigen presentation in major histocompatibility complex (MHC) class II. FRCs can be divided into various subsets, with specific markers, functions, and locations. FRCs located in the T\u2010cell zone (TRCs) can express genes for antigen presentation in MHC class\u2010II, for example,\n                    <jats:italic>H2\u2010Ab1<\/jats:italic>\n                    and\n                    <jats:italic>Cd74<\/jats:italic>\n                    , as well as the immune inhibitory ligand\n                    <jats:italic>Cd200<\/jats:italic>\n                    . However, whether this can be linked to MHC class\u2010II protein expression and thus tolerance is unknown. By combining scRNAseq on murine FRCs with protein staining for extracellular MHC class\u2010II, we confirm that murine TRCs have the highest MHC class\u2010II transcript levels, while protein levels are elevated in multiple FRC subsets. Gene expression for MHC class\u2010II, as well as\n                    <jats:italic>Bst1<\/jats:italic>\n                    and\n                    <jats:italic>Cd200<\/jats:italic>\n                    , gradually increases along the pseudotime trajectory, with TRCs representing the end, indicating maturation. Finally, we validated in fresh LN cell suspensions that MHC class\u2010II protein expression is associated with murine BST1\n                    <jats:sup>+<\/jats:sup>\n                    FRCs, independent of CD200, and with human BST1\n                    <jats:sup>+<\/jats:sup>\n                    CD200\n                    <jats:sup>+<\/jats:sup>\n                    TRCs. This mature FRC subset, equipped to maintain peripheral tolerance, could be an interesting target for therapies against autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1002\/eji.70086","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T12:41:46Z","timestamp":1762778506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced MHC Class\u2010II Expression in Fibroblastic Reticular Cells Associates with Maturation"],"prefix":"10.1002","volume":"55","author":[{"given":"Janna E. 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