The Erikson laboratory is dedicated to the examination of immune cell activation and regulation. Because a hallmark of autoimmune disease is the inappropriate activation of self-reactive lymphocytes, one research objective has been to define the cellular and molecular interactions influencing self-reactive lymphocytes in healthy versus autoimmune settings. The focus has been on autoantibody producing B cells, on the role that T cells play in modifying B cell stimulation and differentiation, and on dendritic cells that are key initiators and modifiers of immune responses. To dissect the role that these cell types play in lymphocyte activation as well as tolerance to "self," models have been developed that facilitate tracking the phenotypic and migratory status of self-reactive cells.
Recent studies have investigated the activation potential of autoreactive B cells in healthy versus autoimmune settings to a variety of T cell dependent as well as independent stimuli. In collaboration with Dr. Caton's laboratory at The Wistar Institute, the Erikson lab has documented that T cell help not only drives autoreactive B cell maturation and entry into the B cell follicle, but also leads to autoantibody secretion, one of the consistent features of autoimmunity. Defining the processes that release self-reactive B cells from their tolerant state is critical to the understanding and eventual treatment of autoimmune disease.
[In the figure at the left: Immunohistology of lungs from an Influenza-infected BLIMP-1-YFP mouse (d38p.i.) depict the location of B220+ B cell clusters (red) and YFP+ plasma cells (yellow).]
Interestingly, if T regulatory cells are provided in vivo along with T helper cells, early B cell activation ensues but autoantibody production is suppressed. Thus, the generation of T regulatory cells can be one strategy to maintain B cell tolerance in the face of T cell activation. Such a scenario may be occurring at early stages in autoimmunity where extensive T cell activation has been documented but is actively being controlled.
Despite the development of effective vaccines, respiratory tract (RT) infections remain a major health problem worldwide. Epidemiological and experimental data show that while influenza A viruses (IAV) alone can cause severe illness, bacterial co-infections often lead to higher morbidity and mortality rates. Pathogen-specific antibodies (Abs), induced by infection or vaccination, are key mediators of protection against influenza yet the impact of co-infection on the anti-viral B cell response is almost completely unknown. In a second line of research, the Erikson lab has developed a mouse model to interrogate the B cell response to IAV infection in the context of Streptococcus pneumoniae (Sp) co-infection. Using mouse models in combination with unique tools to track anti-viral B cells, they are probing the impact of co-infection-induced signals on lymphocyte differentiation programs underlying the induction and maintenance of protective anti-viral B cell immunity. They are testing the hypothesis that bacterial co-infection alters the generation and maintenance of anti-viral B cell immunity at critical checkpoints in B cell differentiation that are controlled by CD4+ T helper and regulatory cells and the inflammatory milieu.
[Above: Immunohistochemistry of lungs from an Influenza-infected mouse (d33p.i.) shows the organization of germinal center B cells (GL7+IgD-) and CD4+ T cells in iBALT (inducible bronchus-associated lymphoid tissue) structures.]