Session V: Networking: immune cells outside their comfort zone
Friday March 31, after the coffee break
11.00 Burkhard Ludewig, St. Gallen, Switzerland
“Stromal cell - B cell interaction”
Fibroblastic stromal cells (FSCs) determine structure and function of classical secondary lymphoid organs (SLOs). These non-hematopoietic cells are also present in non-classical SLOs called “milky spots” of the omentum which function as immune surveillance hubs of the peritoneum; however their identity and functional capacity during immune responses have remained unknown. Using targeted ablation of innate immunological sensing in CCL19-expressing FSCs, we found that MyD88-dependent signaling in omental immune-stimulating fibroblasts is required for swift myeloid cell recruitment and subsequent CD4+ T cell-dependent B cell activation during peritoneal bacterial infection. Moreover, in order to elucidate the cellular composition and molecular regulation of B cell follicle FSCs in lymph nodes, we have generated a novel reporter mouse that permits cell-specific tracing and manipulation of CXCL13-expressing FSCs. Data will be shown that describe the reorganization of follicular dendritic cells in the germinal center (GC) light zone in secondary B cell follicles revealing that the entire infrastructure of CXCL13-expressing FSCs undergoes a dynamic remodelling following viral infection. Moreover, deletion of the LTbR in CXCL13-expressing cells resulted in impaired differentiation of all B cell zone FSCs precipitating attenuated GC B cell and follicular helper T cell responses during viral infection. Together, our data illuminate the FSC composition of the B cell follicle and highlight the B cell follicle fibroblastic cell compartment as a central player for orchestrating B cell responses in classical and non-classical SLOs.
11.45 Reina Mebius, Amsterdam, The Netherlands
"Antigen presentation by lymph node stromal cells"
Dept. Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, the Netherlands.
Stromal cells are crucially involved in the formation of lymph nodes through interacting with hematopoietic lymphoid tissue inducer cells (LTi cells). Once these structures are formed, lymph node stromal cells remain critical for organizing specialized microenvironments within lymph nodes, which are regulating B-T-cell interactions. Furthermore, they shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8+ T cells and MHC-II-dependent anergy of CD4+ T cells. We showed that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of MHC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4+ as well as CD8+ T cells became activated, ultimately resulting in transplant rejection. MHC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of Tregs with specificity for the self-antigen. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate control of self reactive cells. In future studies we will determine whether this mechanism is still properly controlling the adaptive immune system in auto-immune diseases.