The findings, reported in the Aug. 26 issue of the journal Nature, will help scientists better understand two things: how the body is able to mount a strong immune defense against foreign attackers, and how cancers, particularly lymphomas, develop and might be prevented.
B lymphocytes, or B cells, are the immune-system cells responsible for producing antibodies proteins that recognize, bind to, and neutralize viruses and other harmful pathogens. Since there is a huge diversity of pathogens in the environment more than our genomes could possibly anticipate and encode for -- the antibody response has to be very fluid and adaptable. The human immune system handles antibody diversification through selective mutations to specific stretches of DNA in B cells that encode immunoglobulins, the proteins from which antibodies are made. Mutations in these gene segments to the so-called variable regions -- give our B cells the ability to make unique, specialized antibodies with high affinity for a specific invader.
This mutation process, known as somatic hypermutation, is known to require an enzyme called activation-induced cytidine deaminase (AID). But how AID targets the variable region of the immunoglobulin genes -- while leaving the rest of the genetic material in the B cell untouched -- has been a mystery.
In the biochemical study reported in Nature, the Children's Hospital Boston researchers discovered that another protein, known as replication protein A (RPA), interacts with AID, attaches to it, and directs AID to the specific segment of the B cell's DNA required for a tailored immune response. The study details
Contact: Aaron Patnode
Children's Hospital Boston