New Mechanism Found in Immune Response, Antibody Production
A critical step in the immune response occurs when B cells and helper T cells meet and exchange information. Researchers at National Jewish Medical and Research Center and the University of Colorado Denver (UCHSC) have discovered a new signal that promotes the activation of B cells and release of antibodies following this exchange. They also found a surprising, dual role for a pair of molecules in the signal pathway. The findings could lead to a better understanding of the causes underlying immune diseases. The researchers, led by Dr. John Cambier, Professor and Chairman of the Integrated Department of Immunology at National Jewish and UCHSC, published their findings in the February 23, 2001, issue of Science.
On their surfaces B cells express major histocompatibility (MHC) class II molecules associated with antigenic peptides, which bind to a receptor on helper T cells. It has long been known that this interaction induces the helper T cells to promote B-cell activation. In a series of experiments, Dr. Cambier and his colleagues showed that information flows both ways. The interaction causes the MHC/antigen complex to deliver an activation signal to the B cell itself.
"It's a bi-directional signal," said Dr. Cambier. "Upon their association, both TCR and MHC/antigen transduce signals that activate the T cell and B cell respectively. The consequence is a proliferation of both partners. It is possible that failure of this mechanism is an underlying cause of autoimmunity and immunodeficiencies." Future studies will address this possibility and the importance of this bi-directional signal in the immune response.
The researchers also found that a pair of molecules, known as CD79a and CD79b, associates with the MHC/antigen complex and transduces its signal to the B cell. Surprisingly, this molecular pair is involved in earlier signal, one that primes the B cell for its eventual activation. This is the first time that two receptors, triggering separate, sequential responses, have been shown to use the same transducer molecule.
"From an evolutionary point of view, it is an economic use of resources, a pretty intelligent thing to do," said Dr. Cambier. Dr. Cambier suspects that this may be a common theme in signal transduction, and that researchers could find many more examples of it in the future.
