Possible new treatment pathway for B cell diseases

18 May 2015

B lymphocytes.

Image: B lymphocytes.

Francis Crick Institute researchers have uncovered a new signalling pathway that is essential for the survival of mature B lymphocytes, the cells which make antibodies in an immune response. Targeting this pathway may lead to potential new treatments for autoimmune diseases driven by B cells and certain types of B cell cancer.

Dr Steve Ley of the Crick (currently based at Mill Hill)  explained: "The survival of mature B cells depends on a cytokine called BAFF (B cell activating factor) which stimulates a protein on their surface called the BAFF receptor (BAFF-R).

In mice lacking BAFF or BAFF-R, mature B cells fail to develop. Similarly, blocking BAFF results in the rapid loss of mature B cells in mice and humans."

Previous work showed that stimulation of BAFF-R activates two different survival signalling pathways in mature B cells. In this study, the authors identified a third signalling pathway activated by stimulating BAFF-R - called the ERK5 MAP kinase pathway. This pathway is essential for mature B cell survival and for maintaining correct numbers of these cells.

Dr Ley concluded: "Our results suggest that the development of drugs to specifically target the ERK5 MAP kinase pathway in B cells might be an alternative treatment approach for systemic lupus erythematosus, a B cell-driven autoimmune disease that can be treated with BAFF antibodies. Blocking ERK5 signalling might also offer new treatments for certain types of B cell cancer that depend on BAFF for their survival."

The paper, BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival, is published in the Journal of Experimental Medicine.

  • Scientists have uncovered a potential new treatment pathway for autoimmune diseases driven by immune cells called B cells.
  • Systemic lupus erythematosus (SLE) is an autoimmune disease in which a patient's immune system makes antibodies that attack proteins in their own body and cause inflammation in many internal organs, skin, blood vessels and nervous system. It's often characterised by flare-ups and remissions.
  • This work was funded by the Medical Research Council, the Lymphoma Research Foundation in the USA and the Bettencourt-Schueller Foundation in France.