BOSTON As elite soldiers of the body's immune response, B cells serve as a vast standing army ready to recognize and destroy invading antigens, including infections and cancer cells. To do so, each new B cell comes equipped with its own highly specialized weapon, a unique antibody protein that selectively binds to specific parts of the antigen. The key to this specialization is the antigen-binding region that tailors each B cell to a particular antigen, determining whether B cells survive boot camp and are selected for maturation and survival, or wash out and die.
Now, using high-throughput sequencing technology and computational and systems biology, investigators from Beth Israel Deaconess Medical Center (BIDMC) have discovered that B cells can be selected for survival independent of their antigen binding regions. Described online this week in the journal Proceedings of the National Academy of Sciences (PNAS), the findings add a surprising new dimension to the understanding of antibody repertoires each individual's complement of millions of B cells -- and the potential for shaping these repertoires to better fight disease.
"B cells play essential roles in vaccination, infection, autoimmunity, aging and cancer," explains senior author Ramy Arnaout, MD, DPhil, an investigator in the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School whose work focuses on the emerging field of high-throughput multimodality immunology, also known as immunomics. "We were surprised and excited to find that B cell survival could be influenced by a non-antigen-binding region of the antibody, specifically the 'elbow' region that connects the antigen-binding regions to the signaling domain."
Each new B cell makes its own unique antibody by mixing and matching from a set of a few hundred genes, taking one each from subsets called V, D and J. The most diverse part of an antibody is the region where th
|Contact: Bonnie Prescott|
Beth Israel Deaconess Medical Center