Posted on May 12, 2017, 6 a.m.
Newly identified cells reveal why more women are afflicted by autoimmune diseases than men.
National Jewish Health researchers have pinpointed one of the causes for autoimmune diseases such as multiple sclerosis, Crohn's disease and lupus. The findings were recently publicized in the April edition of Journal of Clinical Investigation. This breakthrough is important as it helps explain why females endure autoimmune disease at a higher frequency than their male counterparts. It also suggests a therapeutic target for the prevention of autoimmune diseases in human beings.
About the Findings
The results of the research prove Age-associated B Cells, referred to as “ABCs”, serve to drive autoimmune disease. The research team demonstrated the transcription factor T-bet within B cells causes the development of ABCs. When T-bet within B cells was deleted, mice inclined to develop autoimmune diseases stayed healthy. It is believed the same process takes place in human beings who suffer from autoimmune diseases. In particular, these autoimmune diseases tend to occur in elderly women.
About Autoimmune Diseases
Autoimmune diseases occur when the immune system combats and destroys its host's organs and tissues. A wide array of autoimmune diseases affect millions of individuals across the United States. Many autoimmune diseases like multiple sclerosis, rheumatoid arthritis and lupus impact women between two and 10 times as much as men. All in all, around 80 percent of autoimmune patients are female. Unfortunately, no cure for autoimmune disease exists at the moment.
B cells are vitally important in the context of autoimmune diseases. Research previously conducted by the National Jewish Health team pinpointed a subset of B cells that compile in autoimmune patients, autoimmune mice and older female mice. These cells were named “Age-associated B cells”. The scientific community refers to them as "ABCs".
Additional research determined the transcription factor T-bet performed a critically important role in the generation of ABCs. Transcription factors connect to DNA within cells and spur the expression of one or many genes. The research team believes T-bet manifests within cells when a specific group of B-cell receptors are stimulated. This group is made up of Interferon-gamma, TLR7 and the B-cell receptor.
The National Jewish Health research team made use of genetic and breeding techniques to prevent autoimmune-prone mice from expressing T-bet within their B cells. This prevented ABCs from appearing. The mice remained in good health. Mice with T-bet within B cells had an 80 percent rate of kidney damage. The percentage fell to 20 for mice deficient in T-bet. Three-quarters of mice with T-bet within B cells perished by the 12-month mark. Exactly 90 percent of mice deficient in T-bet survived a full year.
The findings are important as they are the first evidence that ABCs are drivers of autoimmune disease rather than merely a link to autoimmune disease. ABCs have drawn significant interest since being discovered six years ago. The National Jewish Health research team has expanded its analysis of ABCs outside of autoimmune disease. They are currently studying ABCs involvement in chronic beryllium disease, hypersensitivity pneumonitis and sarcoidosis.
Kira Rubtsova et al, B cells expressing the transcription factor T-bet drive lupus-like autoimmunity, Journal of Clinical Investigation (2017). DOI: 10.1172/JCI91250