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Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors

Kreuzaler, Matthias and Rauch, Melanie and Salzer, Ulrich and Birmelin, Jennifer and Rizzi, Marta and Grimbacher, Bodo and Plebani, Alessandro and Lougaris, Vassilios and Quinti, Isabella and Thon, Vojtech and Litzman, Jiri and Schlesier, Michael and Warnatz, Klaus and Thiel, Jens and Rolink, Antonius G. and Eibel, Hermann. (2012) Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. Journal of immunology, Vol. 188, H. 1. pp. 497-503.

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Official URL: http://edoc.unibas.ch/dok/A6006515

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Developmental and Molecular Immunology (Rolink)
UniBasel Contributors:Rolink, Antonius G.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Assoc. of Immunologists
ISSN:0022-1767
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:14
Deposited On:26 Apr 2013 07:00

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