Age-associated B cells found to contribute to autoimmune disorder prevalence in women.
It is well understood that women are more likely than men to develop certain autoimmune disorders, such as multiple sclerosis. Despite many studies dedicated to determining the underlying causes of this occurrence, it has largely remained a mystery.
The authors of a study published by the Journal of Clinical Investigation have discovered a potential trigger for autoimmune disorders, including lupus, Crohn’s disease, and multiple sclerosis, which may explain the high incidence of these conditions among women.
"Our findings confirm that Age-associated B Cells (ABCs) drive autoimmune disease," said researcher Kira Rubtsova, PhD. "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."
Autoimmune disorders occur when the immune system attacks its own organs and often results in painful and debilitating symptoms. Lupus, rheumatoid arthritis, and multiple sclerosis affect women 2 to 10 times as often as men, according to the study.
Previously, the authors discovered that ABCs—a type of B cells—accumulate in patients with autoimmune disorders, as well as elderly mice and mice with autoimmune disorders. Additional research revealed that the T-bet transcription factor played a role in ABCs.
Transcription factors bind to DNA in cells and drive expression of multiple genes. The authors believe that T-bet enters cells when the TLR7, interferon-gamma, and the B-cell receptor, which all live on the surface of B-cells, are stimulated, according to the study.
To further explore this finding, the investigators created mouse models that were prone to developing autoimmune disorders and some that did not express T-bet inside of their B cells. These mice did not have ABCs and were observed to remain healthy during the study.
While 80% of mice that expressed T-bet developed kidney damage, the authors found that only 20% of mice without T-bet experienced kidney damage, according to the study.
Approximately 75% of mice expressing T-bet in their B cells died within 12 months, while nearly all T-bet deficient mice survived 12 months.
These findings suggest that ABCs may play a significant role in autoimmune disorders, but additional studies are needed to confirm the link.
The authors first discovered ABCs in 2011, and have expanded their studies to include the role of ABCs play in sarcoidosis, hypersensitivity pneumonitis, and chronic beryllium disease, according to the study.
"Our findings for the first time show that ABCs are not only associated with autoimmune disease, but actually drive it," Dr. Rubtsova concluded.