Identification of a new cell type regulating antibody responses
A study by the research group of Prof. Sanjiv Luther at the Department of Biochemistry has identified a new fibroblast cell type within the lymph node medulla that is responsible for the survival of antibody-producing plasma cells. This study has been published in PNAS on July 2nd 2018.
Lymph nodes are lymphoid organs where T and B lymphocytes get activated to become effector cells, which includes the generation of plasma cells that represent a critical arm of our host defense system. During an immune response to infectious agents, such as bacteria and viruses, large numbers of these plasma cells develop, with many staying within lymph nodes for several days in so called 'survival niches' found within the medulla. There they secrete large amounts of antibodies that prevent the systemic spread of pathogens. Occasionally, these plasma cells develop in response to non-infectious antigens, either from the environment in the case of allergens, or from the body itself often leading to disease-causing antibody responses.
While several molecules promoting plasma cell survival have been identified, the niche cells supporting this process have remained elusive. A collaborative study between the research group of Professor Sanjiv Luther and Dr. Pascal Schneider at the Department of Biochemistry, FBM, and other research groups in Paris and in Birmingham (UK), has identified fibroblastic stromal cells of the lymph node medulla as critical cells responsible for the survival of plasma cells, and for the development of the structure and organization of the niche in which they reside.
These fibroblasts are distinct from fibroblasts in other lymph node compartments and form a plasma cell survival niche together with hematopoietic cells such as macrophages. In addition to providing cytokines such as IL-6 that promote plasma cell survival and function, these fibroblasts form a 3-dimensional cell network that guides the migration and localization of plasma cells. While this study was performed on murine lymph nodes, a similar fibroblast cell type was uncovered in human lymph nodes.
These discoveries shed a new light onto fibroblasts and their site-specific specialization. Besides playing important roles in maintaining tissue structure, they also form distinct microenvironments within lymphoid organs and directly regulate immune responses. Finally, the identification and characterization of this particular fibroblast subset may help to design intervention strategies to target the niche cells or their factors in the context of allergies or antibody-dependent autoimmune diseases.
par Slavica Masina