Journal
SCIENCE
Volume 297, Issue 5589, Pages 2066-2070Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1073924
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- PHS HHS [P01-A36529] Funding Source: Medline
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Somatically mutated high-affinity autoantibodies are hallmark of some autoimmune diseases, including systemic lupus erythematosus. It has long been presumed that germinal centers (GCs) are critical in autoantibody production, because they are the only sites currently believed to sustain high rate of somatic hypermutation. Contrary to this idea, we found that splenic autoreactive B cells in autoimmune MRL.Fas(lpr) mice proliferated and underwent active somatic hypermutation at the T zone red pulp border rather than in GCs. Our results implicate this region as an important site for hypermutation and the loss of B cell self-tolerance.
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