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Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599
Understanding the regulation of B lymphocytes specific for self-Ags
targeted in human and murine systemic lupus erythematosus, such as the
ribonucleoprotein Smith Ag (Sm), is crucial to understanding the
etiology of this autoimmune disease. To address the role of B cell
receptor affinity in the regulation of anti-Sm B cells, we
generated low-affinity anti-Sm transgenic mice by combining the
anti-Sm 2-12H transgene with a V
8 transgene. In
contrast to 2-12H transgenic mice, in which anti-Sm B cells are
predominantly splenic transitional, and peritoneal B-1, low-affinity
anti-Sm B cells are long-lived B-2 cells and are found in the
spleen, lymph nodes, and peritoneum. However, they are unresponsive to
LPS in vitro, indicating that they are anergic, although they do not
down-regulate IgM and are not excluded from follicles even in the
presence of nonautoreactive B cells. Thus, low-affinity anti-Sm B
cells appear to have a partial form of anergy. Interestingly, these
cells have elevated levels of MHC class II and CD95, but not CD40,
CD80, or CD86, suggesting that they are poised to undergo deletion
rather than activation upon T cell encounter. These data identify
anergy as a mechanism involved in anti-Sm B cell
regulation.
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