When foreign pathogens, such as bacteria or a virus, enter our body, our immune system responds in a concerted effort to eliminate them. B cells produce antibodies that recognize markers (called antigens) on the surface of the invaders; these antibodies are then used to tag foreign pathogens for destruction.

B cells typically require interaction with T cells for full activation and antibody production, which is critical to overcoming an infection. But there are some cases where the T cells are not required. Now, researchers have figured out how this works—and discovered that it relies on the remains of long-dead viruses that litter our genomes.

Large, repetitive sugar structures that are often found on the surface of bacteria and viruses are the key to activating antibody production without the help of a T cell. These sugary structures engage proteins called B cell receptors, which activate the B cells. B cells then grow, forming short-lived cells that produce antibodies and long-lived memory cells that will recognize the same invader upon subsequent infection.

Until recently, researchers have had little understanding of the processes that enable B cells to become activated in the absence of T cell mediation. After exposing mice to an antigen that B cell receptors respond to without T cell activation, researchers monitored the production of antibodies. From these studies, it was apparent that the chemical activates a signaling cascade that ends up making RNA from what are called endogenous retroviruses. Endogenous retroviruses are remnants of past infections that have been incorporated into our DNA.

The RNA made from these viruses then activates B cells through two distinct pathways. In the first pathway, the RNA directly triggers an antiviral signaling pathway. In the second pathway, the RNA is reverse transcribed into DNA, which triggers an antiviral pathway. This pathway later activates interferon genes, producing signaling molecules that evoke a general response to a foreign pathogen. Ultimately, these sensors provide signals that promote the activation and expansion of antigen-specific B cells, which produce the specific antibodies.

Researchers were able to confirm the importance of these pathways using mice that were deficient in critical signaling proteins or by using chemicals that blocked the copying of the RNA into DNA.

Further studies were performed to gain a better understanding of the types of pathogens that activate this pathway. These demonstrated that when antigens from Streptococcus pneumonia and its commercial vaccine Pneumovax are used, endogenous retroviral RNA activates B cells using the second pathway.

These studies suggest that dead viruses are critical for specific response of B cells to this type of surface marker in the absence of T cell mediation. Ongoing work is looking into whether the location of B cells in the body influences the ability to activate this antibody-production pathway. But this study has also highlighted how evolution has harnessed past viral infections to defend itself against new infections.

Science, 2014. DOI: 10.1126/science.1257780 (About DOIs).