title: Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia.
abstract: B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice.
authors.affiliation: From the Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Kowalczyk-Quintas
authors.affiliation: From the Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Sonia
authors.initials: S
authors.lastname: Schuepbach-Mallepell
authors.affiliation: From the Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Michele
authors.initials: M
authors.lastname: Vigolo
authors.affiliation: From the Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Laure
authors.initials: L
authors.lastname: Willen
authors.affiliation: From the Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Aubry
authors.initials: A
authors.lastname: Tardivel
authors.affiliation: From the Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Cristian R
authors.initials: CR
authors.lastname: Smulski
authors.affiliation: Biogen, Cambridge, Massachusetts 02142.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Zheng
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gommerman
authors.affiliation: Merck KGaA, D-64293 Darmstadt, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Hess
authors.affiliation: INSERM UMR S1109, University of Strasbourg, 67085 Strasbourg, France.
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: Department of Immunology, Monash University, Melbourne 3004, Australia, and.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.affiliation: Adipogen Life Sciences, CH-1066 Epalinges, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Donzé
authors.affiliation: From the Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland, pascal.schneider@unil.ch.
authors.forename: Pascal
authors.identifier: 0000-0003-0677-9409
authors.initials: P
authors.lastname: Schneider
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D006965:Hyperplasia; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D018345:Mice, Knockout
chemical_list: D000906:Antibodies; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; C505720:Tnfsf13b protein, mouse
keywords: BAFF; antibody; cytokine; immunology; lymphocyte; receptor