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Canadian researchers have discovered an overlooked gene that plays a major role in the development of antibodies, which help the immune system recognize and fight viruses including SARS-CoV-2, bacteria, and other causes of infectious disease.

The gene — FAM72A — facilitates the production of high-quality antibodies by enabling the effect of an enzyme called AID (for Activation-Induced Deaminase), the researchers showed.

Immunologists have known for two decades that AID is essential to produce antibodies capable of clearing infections, but the full mechanism of its effect has remained unknown.

“Our findings answer the long-standing question of how AID does its work,” said Alberto Martin, a professor of immunology at the University of Toronto’s Temerty Faculty of Medicine.

“FAM72A helps AID to promote mutations in antibody genes that are essential for the development of effective antibodies,” he added.

Genetic mutations that lead to lasting changes in DNA occur through a process called mutagenesis. In the context of antibody development, mutagenesis unfolds largely through the AID-driven mechanisms called somatic hypermutation and class switch recombination — both of which help antibodies gain the diversity and potency they need to counter a wide range of pathogens.

The results published in the journal Nature will help researchers better understand antibody development broadly, but they also have implications for cancer.

Uncontrolled mutagenesis in B cells that produce antibodies is linked to B cell lymphoma, and FAM72A is present at very high levels in other cancers such as gastrointestinal, breast, lung, liver, and ovarian cancers.

“Our data show that high levels of FAM72A promote mutations in antibody genes, so increased levels of FAM72A could spur cancer development, progression, or drug resistance by increasing mutagenesis, a Martin said.

Martin’s team is now exploring those possibilities. Intriguingly, unlike other mammals, humans have four gene versions of FAM72A and their roles in cancer and antibody production are still unknown.

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