Maturation of Lymph Node Fibroblastic Reticular Cells from Myofibroblastic Precursors Is Critical for Antiviral Immunity

Abstract

The stromal scaffold of the lymph node (LN) paracortex is built by fibroblastic reticular cells (FRCs). Conditional ablation of lymphotoxin-β receptor (LTβR) expression in LN FRCs and their mesenchymal progenitors in developing LNs revealed that LTβR-signaling in these cells was not essential for the formation of LNs. Although Tcell zone reticular cells had lost podoplanin expression, they still formed a functional conduit system and showed enhanced expression of myofibroblastic markers. However, essential immune functions of FRCs, including homeostatic chemokine and interleukin-7 expression, were impaired. These changes in Tcell zone reticular cell function were associated with increased susceptibility to viral infection. Thus, myofibroblasic FRC precursors are able to generate the basic Tcell zone infrastructure, whereas LTβR-dependent maturation of FRCs guarantees full immunocompetence and hence optimal LN function during infection. •Novel transgenic mouse model that targets FRCs in adult lymph nodes•FRC-specific ablation of the LTβR did not abrogate LN development•Myofibroblastic FRC precursors generate the basic infrastructure of the adult LN•LTβR-mediated FRC maturation is critical for the maintenance of immunocompentence. © 2013 Elsevier Inc.