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Women Get Autoimmune Disease More, B Cells May Be Why


Of the nearly 24 million Americans who suffer with an autoimmune disease, the majority are women. The findings of a new study suggest that a type of immune system B cells may be a reason why women experience these disorders more than men.

B cells may hold a key to autoimmune disease

Autoimmune diseases, of which there are more than 80 different types, are conditions in which the immune system fails to distinguish between self and what’s foreign. This causes the body to make autoantibodies that attack normal, healthy cells by mistake.

At the same time, regulatory T cells fail to keep the immune system running properly, and the resulting damage to the body is an autoimmune disease. The part of the body affected depends on the type of autoimmune disease. Some of the conditions include multiple sclerosis, rheumatoid arthritis, lupus, celiac disease, type 1 diabetes, and inflammatory bowel disease, among others.

At National Jewish Health, researchers discovered a previously undescribed type of B cell while they were studying X-chromosome genes in healthy male and female mice. The B cells produce autoantibodies that attach to and attack the body’s tissues.

Of special interest was that these cells were found in higher levels in elderly female mice, mice prone to autoimmune disease, and humans with autoimmune diseases. In healthy male mice, however, the B cells remained at a constant low level.

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The B cells increase as healthy female mice grow older, thus the researchers named their discovery Age-associated B Cells (ABCs). According to senior author Philippa Marrack, PhD, professor of immunology at National Jewish Health, “we believe these cells could be useful in the diagnosis and treatment of autoimmune diseases, and may help us understand general mechanisms underlying autoimmunity.”

The researchers were also able to detect elevated ABC levels before disease developed or autoantibodies were evidence, which suggests these B cells could help clinicians detect autoimmune diseases in their earliest stages. They also discovered that when they depleted the ABCs in mice, levels of autoantibodies declined, which indicates B cell depletion could be a treatment for autoimmune diseases. To that end, National Jewish Health has applied for a patent on the method to deplete the B cells to treat autoimmune disease.

Further evidence of an association between the ABCs and females is that activation of the B cells requires stimulation of TLR7, a cell surface receptor. The gene for TLR7 is on the X chromosome, of which women have two and men, one. In some women, the X chromosome expresses elevated levels of some X chromosome genes, such as TLR7.

This dual association—that these B cells appear more often in females and that their activation depends on a gene that women have more of—is an important find. “This could help us understand why women suffer many autoimmune diseases more often than men,” said Anatoly V. Rubtsov, PhD, a postdoctoral fellow at National Jewish Health and first author of the study.

National Jewish Health

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