B cells, a type of white blood cell, are a vital part of our immune system. One of their functions is to make antibodies to fight infections. Now, scientists at the Medical Research Council's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute) have discovered that survival of B cells depends on unexpected cross-talk between two proteins on their surface that were previously thought to be independent of each other.
The number of B cells in our bodies remains constant even though new cells are continuously made in our bone marrow and other cells are lost as they change into a different type of cell that releases antibodies. The correct number of B cells is maintained by carefully regulated survival signals.
Two proteins on the surface of B cells are known to play a large part in their survival. The first is called the BAFF receptor - it binds to BAFF (B-cell activating factor), another important immune system protein, and sends a signal to the B cell that's critical for its survival.
The second is the B-cell antigen receptor, which binds antigens such as those on infectious organisms that get into our bodies. When the B-cell antigen receptor binds an antigen, it sends a signal to the B cell to change into an antibody-releasing cell (meaning that this B cell is lost from the pool).
Victor Tybulewicz and colleagues at NIMR worked with collaborators at the University of Dundee and GlaxoSmithKline in Stevenage.
Dr Tybulewicz explained: "We engineered a new strain of mice in which we were able to specifically remove a critical protein from B cells. Once it is lost, most B cells rapidly die. We then used biochemical methods to show that this key protein sat at the intersection of signals coming from the two cell surface proteins, B-cell antigen receptor and the BAFF receptor.
"The B cell antigen receptor and the BAFF receptor proteins found on the surface of B cells have both previously been shown to be important for the survival of B cells. However our results show that they do not act independently as previously thought, but instead are closely connected biochemically," he added.
"B cells are the white blood cells that produce antibodies. In many autoimmune diseases such as rheumatoid arthritis it has been shown that depleting B cells from the patient improves the condition. This means that understanding how the survival of B cells is controlled is important, as it will allow more precise interventions to control numbers of B cells. The biochemical connection we have found between these two receptors may be a critical point where new therapeutic drugs could be targeted."
The paper, The BAFF Receptor Transduces Survival Signals by Co-opting the B Cell Receptor Signaling Pathway, was published in Immunity.
