Yale researchers shed light on B cells' involvement in autoimmune diseases like lupus

September 30, 2002

Using genetically altered mice, Yale researchers have generated a clearer picture of the origins of B cells and their involvement in autoimmune diseases such as lupus, rheumatoid arthritis and diabetes.

Published in the September 20 issue of Science, the study, led by Mark Shlomchik, M.D., associate professor of laboratory medicine at Yale School of Medicine, looked at B cells' reactions to its own toxins, known as antigens. B lymphocyte cells normally produce antibodies to viruses and bacteria, which protect against infection. However, when these antibodies are directed toward the body's own components they are called "autoantibodies," which can cause inflammation and autoimmune disease.

"B cells that react with 'self' antigens (autoreactive B cells) are very important in the origins of these autoimmune diseases," said Shlomchik. "These B cells make autoantibodies, and also stimulate white blood cells called autoreactive T lymphocytes that destroy tissues, such as the kidney, joints and skin which are the major organs affected in Lupus and Rheumatoid Arthritis." In normal individuals these B cells are tightly controlled and prevented from making autoantibodies.

Shlomchik said the scientific community has known for 15 years that autoantibodies undergo the same processes that generate memory immune responses to viruses. The most important of these processes is called somatic hypermutation, which refers to changes in the genetic code that produces the antibodies. As a result, every immune response contains many subtle variations that critically increase the breadth and strength of the response. There is no other similar process in any cell in mammals, and in B cells it is thought to occur normally in a unique site called the germinal center. However, until now no one had shown where autoantibodies were generated.

The researchers used a strain of mice that were prone to autoimmune diseases to visualize autoreactive B cells. They found that the autoantibody reaction does not take place in the germinal center as previously thought, but in an unusual area of the spleen.

The team also demonstrated that somatic hypermutation of autoantibodies occurs outside of the germinal center in this unusual part of the spleen. These findings suggest that in lupus and other autoimmune diseases, B cells that create autoantibodies escape normal controls by proliferating and undergoing somatic hypermutation outside of the germinal center, which is the normal location for these processes.
-end-
Other authors on the study included Jacqueline William and Sean Christensen, both MD/Ph.D. students at Yale; and Chad Euler who was a research technician in the Shlomchik lab.

Yale University

Related Rheumatoid Arthritis Articles from Brightsurf:

Reducing dementia in patients with rheumatoid arthritis
The incidence of dementia in patients with rheumatoid arthritis is lower in patients receiving biologic or targeted synthetic disease modifying antirheumatic drugs (DMARDs) than in patients who receive conventional synthetic DMARDs, according to a new study.

Is rheumatoid arthritis two different diseases?
While disease activity improves over time for most rheumatoid arthritis (RA) patients, long-term outcomes only improve in RA patients with autoantibodies, according to a new study published this week in PLOS Medicine by Xanthe Matthijssen of Leiden University Medical Center, Netherlands, and colleagues.

Does the Mediterranean diet protect against rheumatoid arthritis?
Previous research has demonstrated a variety of health benefits associated with the Mediterranean diet, which is rich in olive oil, cereals, fruit and vegetables, fish, and a moderate amount of dairy, meat, and wine.

Reducing corticosteroid use in rheumatoid arthritis
Is the long-term use of glucocorticoids essential in people with chronic inflammatory diseases such as rheumatoid arthritis, or can early discontinuation prevent characteristic side effects?

Rheumatoid arthritis patients under treatment with methotrexate
Patients with rheumatoid arthritis (RA) often suffer from what is referred to as interstitial lung disease (ILD).

Rheumatoid arthritis -- can its onset be delayed or prevented?
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that leads to significant health issues as well as high treatment costs.

Disease burden in osteoarthritis is similar to rheumatoid arthritis
Osteoarthritis (OA) has traditionally been viewed as a highly prevalent but milder condition when compared with rheumatoid arthritis (RA), and some may believe that it is part of a normal aging process requiring acceptance, not treatment.

Prospect of a new treatment for rheumatoid arthritis
An international research group led by Charité -- Universitätsmedizin Berlin has completed testing a new drug to treat rheumatoid arthritis.

Can rare lymphocytes combat rheumatoid arthritis?
Immunologists at Friedrich-Alexander-Universität Erlangen-Nürnberg have demonstrated that ILC2, a group of rare lymphoid cells, play a key role in the development of inflammatory arthritis.

Rheumatoid arthritis meets precision medicine
Scientists are bringing precision medicine to rheumatoid arthritis for the first time by using genetic profiling of joint tissue to see which drugs will work for which patients, reports a new multi-site study.

Read More: Rheumatoid Arthritis News and Rheumatoid Arthritis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.