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.