Development of autoreactive naïve and memory B cells in autoimmune disease

Autoimmune diseases, which are often debilitating and chronic, pose significant challenges to the patients, health-care systems and Society.

For many of these diseases, the aetiologies and underlying mechanisms are poorly understood and effective therapies are lacking.

Our ambition is to build a comprehensive picture of autoimmune disease with the emphasis on the development of autoreactive naïve and memory B cells.

The goal is to translate important observations from our unique murine model of autoimmunity to humans with the autoimmune disease rheumatoid arthritis (RA).

Our hypothesis is that autoreactive B cells are generated in the bone marrow, and as naïve B cells initiate immune reactions that lead to the formation of immunological memory, including autoreactive memory B cells that perpetuates the autoimmune response.

We will dissect the genesis of B cells in the bone marrow from patients with osteoarthritis and RA to determine whether autoreactive B cells are generated, and define autoreactive memory B-cell subsets in peripheral blood from patients with untreated early RA.

We have generated single-cell RNA- and immune repertoire-seq data from bone marrow and memory cells to be analysed by bioinformaticians over the next four years.

We believe that a new paradigm for autoimmune disease development will emerge that will guide the design of new therapeutic interventions and possibly prevent disease progression in persons who are pre-disposed to develop RA.