Researchers at Denver’s National Jewish Health have prevented autoimmune disease in mice prone to a lupus-like illness by eliminating a protein called T-bet. This protein, which helps transform a type of white blood cell into an age-associated B-cell (ABC), may be a possible therapeutic target for treating lupus, multiple sclerosis, Crohn’s disease and other autoimmune conditions.
Their study, “B cells expressing the transcription factor T-bet drive lupus-like autoimmunity,” appeared in the Journal of Clinical Investigation.
About 80 percent of autoimmune patients. This research builds on previous observations that ABCs appear in autoimmune patients as well as in autoimmune and elderly female mice — and that T-bet, a protein that occurs naturally in B-cells and fuels genetic activity, is crucial to the development of ABCs from B-cells.
The team set out to eliminate T-bet in B-cells from mice prone to a lupus-like disease to see whether that would prevent ABCs from appearing and keep the mice from developing lupus. As expected, ABCs did not appear in those mice and the rodents stayed healthy. Only 20 percent of the mice whose T-bet had been eliminated showed kidney damage, compared to 80 percent of the control mice with T-bet in their B-cells.
The survival rate for mice without T-bet was striking: 90 percent of them survived 12 months, while 75 percent of those with T-bet in their B-cells died before reaching their first birthday — demonstrating that this deletion cuts kidney diseases, prolongs survival and delays the appearance of autoantibodies.
“Our findings confirm that age-associated B-cells (ABCs) drive autoimmune disease,” Kira Rubtsova, the study’s first author and a biomedical science instructor at National Jewish Health, said in a press release. “We demonstrated that the transcription factor T-bet inside B-cells causes ABCs to develop. When we deleted T-bet inside B-cells, mice prone to develop autoimmune disease remained healthy. We believe the same process occurs in humans with autoimmune disease, more often in elderly women.”
She added: “Our findings for the first time show that ABCs are not only associated with autoimmune disease, but actually drive it.”
Based on the results, the team hypothesized that coming up with a depleting agent targeting B-cells with T-bet could help patients with lupus and other autoimmune diseases.