Research supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases offers new insight into the cellular mechanisms of systemic lupus erythematosus (SLE), or lupus, a disabling and sometimes life-threatening disease that affects as many as 322,000 Americans, mostly women. The disease occurs when the body's immune system, which is designed to protect it from invaders, mistakenly attacks its own tissues, damaging multiple organ systems.
While this self-directed (autoimmune) response is not well understood, research has established that interactions between different populations of immune cells-B cells and T cells-are involved in the key steps in the development of lupus. The new research provides a better understanding of those reactions, which could potentially lead to better ways to both diagnose and treat the disease.
In healthy people, B cells are made in the bone marrow and produce antibodies (proteins that destroy or aid in the destruction of threats, such as bacteria and viruses). T cells, which are produced in the bone marrow and matured in the thymus, are known to make close contact with B cells, stimulating them to produce antibodies. In people with autoimmune diseases, scientists have suspected that B cells' propensity to excessively produce damaging autoantibodies is dependent on signals and interactions with T cells. NIAMS-supported investigators, however, discovered that B cells can be activated in the absence of T cells.
Using a mouse model of lupus, they found that toll-like receptors (TLRs), molecules on the surfaces of T and B cells which mediate the cells' responses, could be stimulated by an animal's own DNA or RNA. This resulted in the activation and maturation of B cells, the subsequent production of autoantibodies, and, finally, disease in the mice. Activated B cells, in turn, recruit and activate T cells, thus perpetuating the cycle of immune system dysregulation, inflammation and disease.
The new finding brings scientists one step closer to understanding the cellular events that lead to lupus, a disease which has not been clearly defined. They say the results of this work will help explain why B cells are so promising and will add support to the need for further development of B-cell focused treatments for the disease.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov .
Source: Herlands RA , Christensen SR , Sweet RA , Hershberg U , Shlomchik MJ . T Cell-Independent and Toll-like Receptor-Dependent Antigen-Driven Activation of Autoreactive B Cells. Immunity.2008 Aug;29(2):249-60. PMID: 18691914
Prevalence figures for lupus were published in "Estimates of the Prevalence of Arthritis and Other Rheumatic Conditions in the United States " in the January 2008 issue of Arthritis & Rheumatism