In addition, we found that IDC and MDC proteolytic activities were modulated by HIV-1 exposure;
complement-opsonized HIV-1 induced an increased proteasome activity in IDCs. Taken together, these findings indicate that endocytic receptors such as MMR, complement receptor 3, and β7-integrin can promote or disfavor antigen presentation probably by routing HIV-1 into different endosomal compartments with distinct efficiencies for degradation of viral antigens and MHCI and MHCII presentation, and that HIV-1 affects the antigen-processing machinery. “
“The germinal centre (GC) is a specialized microenvironment where high-affinity RNA Synthesis inhibitor antibodies are produced through hypermutation and isotype switching. Follicular dendritic cells (FDCs) are the stromal cells of the GC. The timely BMS-907351 mw expansion and establishment of an FDC network is essential for a protective GC reaction; however, only a few factors modulating FDC development have been recognized. In this study, we report that interleukin-15 (IL-15) enhances human primary FDC proliferation and regulates cytokine secretion. The FDCs express IL-15 receptor complexes for IL-15 signal transduction as well as for specific binding. Moreover, the secretion of chemokines
CCL-2, CCL-5, CXCL-5 and CXCL-8 was reduced by blocking IL-15 signalling while the secretion of other cytokines, and the expression of CD14, CD44,
CD54 (ICAM-1) and CD106 (VCAM-1) proteins remained unchanged. These results suggest that IL-15 plays a crucial role in the development of FDC networks during GC reaction, offering a new target for immune modulation. The germinal centre (GC) is a dynamic microenvironment where protective high-affinity antibodies are produced through extremely rapid B-cell proliferation and extensive modification of their immunoglobulin genes.1–4 The follicular dendritic cells (FDCs) are the stromal cells of the GC.5–7 find more The major function of FDCs is to retain intact antigen–antibody complexes to provide selective signals to GC-B cells expressing the highest affinity antigen receptor.8,9 The FDCs also provide other crucial microenvironmental factors for GC development. They prevent apoptosis of GC-B cells by cellular interaction and stimulate proliferation by providing adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1);9 the anti-apoptotic molecules BAFF/BLys;10 and a number of growth factors, such as 8D6, interleukin-6 (IL-6) and IL-15.11–13 In addition, FDCs secrete chemokines such as CXCL13, to direct the migration of lymphocytes and other bone-marrow-derived cells.14,15 While the functions of FDCs have been investigated, the factors that control FDC development have begun to be identified recently.