期刊
JOURNAL OF IMMUNOLOGY
卷 188, 期 1, 页码 497-503出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1102321
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资金
- European Union [HEALTH-F2-2008-20154]
- German Federal Minister for Research and Technology [BMBF 01 EO 0803]
- German Cancer Fund
- Swiss National Science Foundation
- Jeffrey Modell Foundation
- Eleonora Lorillard Spencer Cenci Foundation
- Czech Ministry of Health [NS 10398-3]
- Fondazione C. Golgi, Brescia
- Italian Association for Primary Immunodeficiencies
The TNF family member protein BAFF/BLyS is essential for B cell survival and plays an important role in regulating class switch recombination as well as in the selection of autoreactive B cells. In humans, increased concentrations of soluble BAFF are found in different pathological conditions, which may be as diverse as autoimmune diseases, B cell malignancies, and primary Ab deficiencies (PAD). Because the mechanisms that regulate BAFF levels are not well understood, we newly developed a set of mAbs against human BAFF to study the parameters that determine the concentrations of soluble BAFF in circulation. Patients with PAD, including severe functional B cell defects such as BTK, BAFF-R, or TACI deficiency, were found to have higher BAFF levels than asplenic individuals, patients after anti-CD20 B cell depletion, chronic lymphocytic leukemia patients, or healthy donors. In a comparable manner, mice constitutively expressing human BAFF were found to have higher concentrations of BAFF in the absence than in the presence of B cells. Therefore, our data strongly suggest that BAFF steady-state concentrations mainly depend on the number of B cells as well as on the expression of BAFF-binding receptors. Because most patients with PAD have high levels of circulating BAFF, the increase in BAFF concentrations cannot compensate defects in B cell development and function. The Journal of Immunology, 2012, 188: 497-503.
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