Targeting B cell activation in autoimmune diseases

The autoimmune disease SLE is complex and currently without a cure, and the current goal with treatment is to minimize organ damage and flares of disease activity and comorbidities such as atherosclerosis. A major problem though, is that when the patients are diagnosed there is already irreversible organ damage.

Still, autoantibodies occur years before disease onset and thus finding B cell directed treatments and novel clinical markers could potentially stop the disease early.

Here, I propose to focus on B cells and bridge knowledge available in the fields of cardiovascular and rheumatology research to find key disease mechanisms for treatment.

An important focus will be studies on B cell activation in the spleen, which is our largest lymphoid organ and the interface with the circulation.

The specific subtypes of B cells that reside here have access to the circulation and this is where a systemic immune response to blood-borne antigens starts.

I propose that part of the imbalance in the immune system leading to systemic inflammatory disease also can be found here.This is a five year project and the majority of the research will be done using mouse models for SLE or atherosclerosis developed and setup in our laboratory. We will use conditionally targeted mice that are available or being made in collaboration.

Also, we will setup novel methods to look at B cell activation including investigation of auto-antigen specific B cells and also metabolic regulation of phagocytes.