14 July 2020
Immune receptors team up to fight infection
Published online 12 April 2012
When infectious agents invade the human body, it is B cells, a type of immune cell, which are the first to respond. Naive B cells first encounter antigens from potentially pathogenic bacteria or viruses, through receptors on their cell surface that send a signal to initiate the development of antibodies to fight infection.
T cells, another type of immune cell, are usually essential for B cells to start developing antibodies. Some antigens, however, trigger a signal that prompts B cells to produce antibodies without the help of T cells. In research published in Nature Communications, Paolo Casali and colleagues examine the mechanism by which B-cell receptors collaborate to ramp up antibody production by exposing them to specific receptor-targeted antigens.
At the early stages of immune response to pathogens, B cells rely on class-switch DNA recombination (CSR), in which specific DNA segments are removed from the antibody-coding region of the chromosome to produce greater diversity in the genetic sequences that encode antibodies. The researchers — including Ahmed Al-Qahtani of the medicine and health sciences department at United Arab Emirates University in Al Ain, UAE — found that signaling of both Toll-like receptors (TLRs) and B cell receptors (BCRs) in B cells is integral to initiate CSR. Activating only one type of receptor yielded little CSR, and thus little antibody against the antigen. When both receptors were activated, antibody production ramped up.
Antibody production depends on BCRs and TLRs each activating separate pathways that increase production of activation-induced cytidine deaminase (AID). Higher AID levels increasingly activate CSR, engaging the B cell in antibody production without the assistance of T cells.
"This sheds light on why patients deficient in molecules that allow TLR or BCR signaling are susceptible to infections," says Casali. These receptors' activity could also provide clues for the design of vaccines against certain pathogens.
- Casali, P. et al. Nature Communications (2012). doi:10.1038/ncomms1769