Protein linked to antibodies also has an antiviral function, researchers show
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In biology, it’s actually possible to teach an old dog a new trick. A new finding from Rockefeller University’s Nina Papavasiliou has shown that a protein called AID, which is involved in creating diversity among immune system antibodies, evolved long before antibodies themselves did — suggesting that its role in the cell today is not the one it originally had.
The body’s immune system encounters thousands of potential attackers throughout the lifetime of an organism, many more than it could possibly encode antibodies for. AID, short for Activation-Induced cytidine Deaminase, is one way B cells, which produce antibodies, generate diversity. By introducing mutations into an antibody’s genes, AID creates a range of antibodies and helps prep the immune system to respond to attackers it has not yet been exposed to. However, antibodies are a fairly new addition to the genome, first showing up in sharks. AID has been around a lot longer than antibodies.
Red flag. When B cells are infected with a virus, they begin to make the AID protein (red) within four to six days, as shown in these time-lapse images. The protein serves to stop sick B cells from dividing and it flags the cell for clearance by other immune cells.
“Antibodies are a result of a transposon that jumped into the shark genome about 300 million years ago,” says Papavasiliou, head of the Laboratory of Lymphocyte Biology. “But AID was present before this, so we wanted to know what it was doing there.”
Papavasiliou’s results, published this summer inImmunity, suggest that AID originally conferred immunity against viruses. Another member of the same protein family, called APOBEC3, had been shown to become active in immune system T cells that were infected with HIV. The protein was packaged with the new HIV virions where it then mutated the virus’s RNA to make it less infectious. Papavasiliou wanted to know if perhaps AID functioned in a similar way in B cells, where it was expressed.
“Normally AID is only expressed in B cells that are rearranging their antibody genes,” says Papavasiliou. “But when we infected B cells with a virus, we saw that those cells began making AID. After this, two things happen: First, those cells that are infected stop proliferating, and second, the cells then become marked for clearance by natural killer cells, part of the immune system that kills virally infected cells.”
Papavasiliou’s data showed that AID’s function in antibody diversity is relatively new, and its function in viral immunity was AID’s original task. Before antibodies, AID was important for restricting the division of virally infected cells and for alerting the rest of the immune system to the cells that were infected, helping the immune system limit the spread of disease. “AID is now the second member of the family to have an antiviral function,” says Papavasiliou. “How exactly it accomplishes these actions is still a big question that we are trying to answer.”
