The ABCs of Autoimmunity

“It’s well-known that autoimmune diseases mostly affect women – in fact, about 80 percent of all autoimmune patients are women,” explains Kira Rubtsova, a researcher and instructor in biomedical science at National Jewish Health. “At the same time, the onset of autoimmunity usually happens during adulthood.” Why are women so disproportionately affected by autoimmune issues? Rubtsova and her colleagues suspected that the female immune system undergoes changes with age that lead to the progression of autoimmunity – changes that the male immune system does not experience. But precisely what are those changes? In the quest to answer that question, Rubtsova’s group discovered age-associated B cells (ABCs).

What are ABCs?

“ABCs are a unique subset of B cells that can be distinguished from other types by the expression of certain molecules. In particular, ABCs express the integrins CD11c and CD11b on their surfaces and contain high levels of transcription factor T-bet, none of which is expressed by other types of B cells.” And when the researchers compared the gene expression profiles of ABCs with those of other B cells, they found hundreds of differentially expressed genes – indicating that ABCs have a unique phenotype and likely a unique function (1).

What do ABCs do?

“ABCs are present at high frequency in lupus-prone mice,” says Rubtsova, “and their appearance coincides with the onset of the disease in these animals.” The team also observed elevated ABCs in human autoimmune disease patients – but, at the time, they weren’t sure whether the appearance of ABCs caused the development of disease or merely coincided with it.

In their recently published study (2), Rubtsova’s team generated mice that are predisposed to developing lupus-like autoimmunity, but lack T-bet expression in B cells (meaning that they cannot generate ABCs). “We have followed the health conditions of these mice over time, comparing them with lupus-prone mice that can develop ABCs,” she says. In the absence of ABCs, the lupus-prone mice were significantly less likely to develop disease. “These data led us to the conclusion that ABCs drive the onset of autoimmunity.”

Could ABCs be diagnostically useful?

“The presence of these cells can be used for diagnostic purposes,” Rubtsova says. It’s possible that, one day, patients suspected of autoimmune disorders could be tested for the presence of ABCs. And if the cells participate in the disease process, it’s also possible that people at risk of developing such disorders might even be screened using ABCs one day, allowing doctors to spot autoimmune diseases before symptoms arise.

But Rubtsova also wants to highlight the therapeutic potential: “These cells can be used as targets for the development of novel therapies that could cure autoimmunity. Because our results indicate that ABCs represent the pathogenic subset of cells, their removal may lead to the amelioration of disease.” One of her team’s next goals is to develop a drug capable of depleting or inactivating ABCs.

In the meantime, many questions remain. How do ABCs promote the development of autoimmunity? Why is T-bet expression so critical for the development of these cells? And why are females more predisposed to developing ABCs and autoimmune diseases?