Australian scientists demystify the role of ‘junk cells’ in the fight against malaria

Researchers at the Australian National University (ANU) have discovered the previously unknown ability of a group of immune system cells, called atypical B cells (ABC), to fight infectious diseases such as malaria.

This discovery provides new insights into how the immune system fights infections and brings scientists closer to harnessing the body’s natural defenses to fight malaria. The research is published in Scientific immunology.

Scientists say ABCs could also play a key role in developing new treatments for chronic autoimmune diseases such as lupus.

According to the researchers, ABC cells have long been associated with malaria because malaria patients have more of these cells in their systems than the general population.

“In this study, we wanted to understand the mechanisms that lead to the creation of ABCs in the immune system, but also find out whether these cells are good or bad for us when it comes to fighting infections,” said l Lead author Dr Xin Gao, from ANU, said.

“Although ABCs are known to contribute to chronic inflammatory diseases and autoimmunity, we have discovered a previously unknown ability of these cells to fight disease. In this sense, ABCs are like a weapon double-edged.

“Contrary to what was once thought, ABCs are not unwanted cells; they are more important than we thought.

“Our research found that ABCs also play a key role in the development of follicular helper T cells. These helper cells generate powerful antibodies that help the body fight malaria parasites.

“Antibodies can block parasites in the blood as they travel from the site of the infectious mosquito bite to the liver, where the infection first becomes established.”

In 2022, malaria killed more than 600,000 people worldwide. Although the disease is preventable and curable, scientists face an uphill battle to find lasting treatments, as malaria parasites continue to find new ways to develop resistance to current therapies.

Using gene editing technology on mice, ANU researchers discovered that a gene called Zeb2 is crucial for ABC production.

“We found that manipulating the Zeb2 gene disrupted the creation of ABCs in the immune system,” said study co-author Professor Ian Cockburn, from the ANU John Curtin School of Medical Research.

“Importantly, we found that mice lacking the Zeb2 gene were unable to control malaria infection.

“Therefore, the results show that ABCs play a crucial role in combating malaria infections.”

Researchers say targeting ABCs could also open the door to new treatments for certain autoimmune diseases such as lupus.

“ABCs also appear in large numbers in many autoimmune diseases, including lupus, which can be life-threatening in severe cases,” Professor Cockburn said.

“By developing a better understanding of the role of ABCs in the immune system and the role of cells in fighting disease, it could bring us closer to one day developing new and more effective therapies.”