title: Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors.
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.
authors: Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
authors: Matthias
authors: M
authors: Kreuzaler
authors: Melanie
authors: M
authors: Rauch
authors: Ulrich
authors: U
authors: Salzer
authors: Jennifer
authors: J
authors: Birmelin
authors: Marta
authors: M
authors: Rizzi
authors: Bodo
authors: B
authors: Grimbacher
authors: Alessandro
authors: A
authors: Plebani
authors: Vassilios
authors: V
authors: Lougaris
authors: Isabella
authors: I
authors: Quinti
authors: Vojtech
authors: V
authors: Thon
authors: Jiri
authors: J
authors: Litzman
authors: Michael
authors: M
authors: Schlesier
authors: Klaus
authors: K
authors: Warnatz
authors: Jens
authors: J
authors: Thiel
authors: Antonius G
authors: AG
authors: Rolink
authors: Hermann
authors: H
authors: Eibel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000097:blood / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000276:immunology*; D007223:Infant; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008875:Middle Aged; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse