Journal
JOURNAL OF IMMUNOLOGY
Volume 167, Issue 4, Pages 1920-1928Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.167.4.1920
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- NIAID NIH HHS [AI34580-05] Funding Source: Medline
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The organization of secondary lymphoid tissues into distinct T and B cell compartments supports proper regulation of an immune response to foreign Ags. In the splenic white pulp, this compartmentalization is also thought to be important in the maintenance of B cell tolerance. Using lymphotoxin-alpha-(LT-alpha)-, TNF-alpha-, or TNFRp55-deficient mice, all with disrupted splenic architecture, we tested whether normal T/B segregation and/or intact follicular structure are necessary for the maintenance of anti-dsDNA B cell anergy. This study demonstrates that anti-dsDNA B cells remain tolerant in LT-alpha (-/-), TNF-alpha (-/-), and TNFRp55(-/-) mice; however, TNF-alpha or a TNF-alpha -dependent factor is required for their characteristic positioning to the T/B interface. Providing a TNF-alpha signal in TNF-alpha (-/-) mice by systemic administration of an agonist anti-TNFRp55 mAb induces the maturation of the anti-dsDNA B cells and their movement away from the T cell area toward the B cell area. Additionally, the agonist Ab induces changes in the follicular environment, including FDC clustering, up-regulation of the CXC chemokine ligand CXCL13, and down-regulation of the CC chemokine ligands CCL19 and CCL21. Therefore, this study suggests that a balance between B and T cell tropic chemokine signals may be an important mechanism for positioning anergic B cells at the T/B interface of the splenic white pulp.
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