The expression by immune B-cells of a protein called T-bet is crucial to promoting production of autoantibodies that recognize and destroy the tissues of one’s own body, finds a new study by researchers at National Jewish Health in Denver.
The study, “B cells expressing the transcription factor T-bet drive lupus-like autoimmunity,” appeared in the Journal of Clinical Investigation. It not only identifies a trigger for autoimmunity, but also suggests a new potential therapeutic target to prevent autoimmune diseases such as multiple sclerosis (MS) and lupus that strike women two to 10 times as often as men. Overall, about 80 percent of autoimmune patients are women.
Previous studies showed that a subset of immune B-cells known as age-related B-cells (ABCs) expresses the T-bet transcription factor, which controls the expression of genes. Interestingly, these ABCs were found to appear in patients with autoimmune diseases and in autoimmune experimental animal models, suggesting that they may play a role in such diseases.
Through genetic manipulation, researchers created autoimmune-prone mice that did not express the T-bet protein. Evaluating the immune cell subsets these mice had in circulation confirmed the absence of ABCs. Researchers weren’t surprised, since these cells require T-bet expression to survive. Strikingly, these mice showed reduced signs of autoimmune disease, they lived longer, and their production of autoantibodies was delayed compared to mice that did express T-bet and had ABCs.
“Our findings confirm that Age-associated B Cells (ABCs) drive autoimmune disease,” National Jewish Health biomedical science instructor Kira Rubtsova and the study’s lead author, 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.”
These results indicate that T-bet expression in B-cells is key the autoimmunity process, contributing to its development or progression.
“Our findings for the first time show that ABCs are not only associated with autoimmune disease, but actually drives it,” said Rubtsova, concluding that targeting T-bet-expressing B cells may therefore be a potential therapeutic strategy for autoimmune diseases.