Medizinische Universität Graz - Research portal
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SHR Neuro Cancer Cardio Lipid Metab Microb
Kreuzaler, M; Rauch, M; Salzer, U; Birmelin, J; Rizzi, M; Grimbacher, B; Plebani, A; Lougaris, V; Quinti, I; Thon, V; Litzman, J; Schlesier, M; Warnatz, K; Thiel, J; Rolink, AG; Eibel, H.
Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors.
J IMMUNOL. 2012; 188(1): 497-503.
Doi: 10.4049/jimmunol.1102321
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Thiel Jens
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- Abstract:
- 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.
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