Expression of MHC I and II and antigen processing genes following INF-γ treatment in fibroblastic reticular cells and double negative cells

Abstract

Abstract Lymph node (LN) is a secondary lymphoid organ with highly organized structure. Fibroblastic reticular cells (FRCs) integrate LN structure, and are characterized by podoplanin expression (PDPN, gp38) and lack of CD31. FRCs are involved in several immune response processes but the mechanism is still under investigation. Another cell population present in LN is a fibroblastic cell lacking PDPN and CD31 expression, called double negative cells (DNCs). FRCs and DNCs are described to control migratory pattern and positioning of immune cells during homeostasis or inflammatory response. We evaluate in human derived FRCs and DNCs the gene expression after IFN-γ-treatment and found up-regulated genes related to antigen processing and MHC class I and II up-regulated. MHC class I is expressed by all nucleated cells and MHC class II constitutive expression is confined to the immune system antigen-presenting cells, but can be induced in several cells types. MHC class II genes control has been described to play a role in eliminting foreign antigens, while minimizing autoreactive responses against self-antigens. MHC class II molecules can fulfill additional functions by triggering a variety of signaling pathways, they can regulate proliferation and maturation to apoptosis. In addition, we were able to demonstrate that HLA-ABC and HLA-DR were increased in the membrane of both FRCs/DNCs derived from different patients/lymph nodes after treatment with IFN-γ. FRCs seem to be more responsive to IFN-γ than DNCs. Furthermore, we have tested the ability of FRCs to internalize particles, showing a functional MHC II pathway.