Age-associated B Cells: Trigger for Autoimmune Disease Identified

Highlights

• Autoimmune disease occurs due to an abnormal response in the immune system of the body.
• Women are more frequently affected with autoimmune diseases like Crohn’s disease, lupus, multiple sclerosis than men, finds study.
• Scientists have now found age-associated B cells (ABCs) to be responsible for triggering the autoimmune disease.

Autoimmune disease develops when the immune system defends the body against the attacking disease. A research team from the National Jewish Health has identified a trigger for autoimmune diseases like lupus, Crohn’s disease and multiple sclerosis. The findings were published in the Journal of Clinical Investigation.

The study also explained why women would suffer from autoimmune disease more frequently than men and also suggested targets to prevent autoimmune diseases in humans.

Kira Rubtsova, Ph.D, instructor in biomedical science at National Jewish Health, said, "Our findings confirm that Age-associated B Cells (ABCs) drive autoimmune disease."

"We demonstrated that the transcription factor T-bet inside B cells cause 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."

Age-associated B Cells (ABCs)
Previous studies have identified a subset of B cells which accumulate in autoimmune patients, autoimmune and elderly female mice. The cells were named as Age-associated B cells or ABCs. The research team also showed that transcription factor T-bet would play a crucial role in the presence of ABC.

Transcription factors may bind to DNA inside cells and help to drive the expression of one or several genes. The research team also found that the T-bet cells would appear inside the cells when a combination of receptors on B-cell surfaces, TLR7, interferon-gamma and B cell receptor are stimulated.

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The research team also eliminated the ability of the mice to express the T-bet inside the B cells by using breeding and genetic techniques. Due to this, there were no ABCs and the mice remained healthy.

Around 80% of the mice with T-bet in the B cells had kidney damage, while only 20% in T-bet-deficient mice.

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75% of the mice with T-bet in the mice cells died by 12 months while around 90% of T-bet-deficient mice survived 12 months.

Dr. Rubstova, said, "Our findings for the first time show that ABCs are not only associated with autoimmune disease, but actually drive it."

Further research on ABCs has expanded to the study beyond autoimmune disease and also investigates the involvement in sarcoidosis, hypersensitivity, pneumonitis and chronic beryllium disease.

Autoimmune Diseases
When the immune system of the body attacks and destroys the organs and tissues of the host, it would result in Autoimmune disease. This would affect millions of people in the United States.

Diseases like lupus, rheumatoid arthritis and multiple sclerosis may affect women about two to ten times as often as men. Around 80% of the women are affected by autoimmune diseases and there is no cure for the disease.

Some of the Autoimmune diseases include

• Alopecia areata
• Autoimmune hepatitis
• Psoriasis
• Grave’s disease
• Myasthenia gravis
• Rheumatoid arthritis
• Multiple sclerosis

References

1. Kira Rubtsova, Anatoly V. Rubtsov, Joshua M. Thurman, Johanna M. Mennona, John W. Kappler, Philippa Marrack. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. Journal of Clinical Investigation, 2017; 127 (4): 1392 DOI: 10.1172/JCI91250
2. Understanding Autoimmune Diseases - (https://www.niams.nih.gov/Health_info/Autoimmune/default.asp )

Source-Medindia