such as "Introduction", "Conclusion"..etc
August 8, 2008 — B cells, the source of
damaging autoantibodies, have long been thought to depend upon T cells
for their activation and were not considered important in the
initiation of autoimmune diseases like lupus or rheumatoid arthritis.
In the Aug. 7 online issue of the journal of Immunity, Yale
University researchers turn this paradigm on its head by showing that
in systemic autoimmune diseases B cells can be activated the absence of
The study suggests new ways to intervene in the immune system's chronic attacks on the body's own tissue.
The findings were surprising because many scientists believed that B
cells remain quiet in autoimmune diseases unless they are stimulated
first by T cells, said Mark Shlomchik, MD, professor of laboratory
medicine and immunobiology at the Yale School of Medicine and senior
author of the study.
"It became a chicken or egg problem. If cooperation between T and B
cells is needed to create an autoimmune disease, who falls off the
fence first, and why?'' Shlomchik said.
Recently this same Yale group along with collaborators at Boston
University discovered an unexpected role in autoimmunity of Toll-like
receptors, previously thought to be stimulated by molecules expressed
on microbial pathogens. Shlomchik and his colleagues showed that they
can also recognize and react to "self" molecules, in particular
mammalian DNA and RNA. When this occurs, these receptors help activate
B cells that make the classical autoantibodies of lupus.
The new Yale study now shows that these signals substitute for T
cells in starting the autoimmune process in B cells. The researchers
propose that once B cells are activated via Toll-like receptors, they
can subsequently recruit T cells and that this can lead to a "vicious
cycle" of chronic autoimmune disease in which the two types of cell
activate each other.
The findings might explain why treatments that target T cells in
autoimmune diseases have fared relatively poorly, while newer
treatments aimed at B cells have shown great promise, he said.
The current study is a direct outgrowth of groundbreaking work
conducted at Yale over the last 15 years that showed that elements of
the innate, or non-specific immune system such as Toll-like receptors,
needed to be triggered before more sophisticated adaptive immune system
of humans and other animals could hone in on specific pathogens.
Other authors on the paper are Robin A. Herlands, Sean R. Christensen, Rebecca A. Sweet and Uri Hershberg.
The research was funded by the NIH Institutes of Arthritis and
Musculoskeletal and Skin Diseases and of Allergy and Infectious
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