title: Survival of Igα-Deficient Mature B Cells Requires BAFF-R Function.
abstract: Expression of a functional BCR is essential for the development of mature B cells and has been invoked in the control of their maintenance. To test this maintenance function in a new experimental setting, we used the tamoxifen-inducible mb1-CreER(T2) mouse strain to delete or truncate either the mb-1 gene encoding the BCR signaling subunit Igα or the VDJ segment of the IgH (H chain [HC]). In this system, Cre-mediated deletion of the mb-1 gene is accompanied by expression of a GFP reporter. We found that, although the Igα-deficient mature B cells survive for >20 d in vivo, the HC-deficient or Igα tail-truncated B cell population is short-lived, with the HC-deficient cells displaying signs of an unfolded protein response. We also show that Igα-deficient B cells still respond to the prosurvival factor BAFF in culture and require BAFF-R signaling for their in vivo maintenance. These results suggest that, under certain conditions, the loss of the BCR can be tolerated by mature B cells for some time, whereas HC-deficient B cells, potentially generated by aberrant somatic mutations in the germinal center, are rapidly eliminated.
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; International Max Planck Research School for Molecular and Cellular Biology, 79108 Freiburg, Germany;
authors: Ella
authors: E
authors: Levit-Zerdoun
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; International Max Planck Research School for Molecular and Cellular Biology, 79108 Freiburg, Germany;
authors: Martin
authors: http://orcid.org/0000-0002-1751-1056
authors: M
authors: Becker
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany;
authors: Roland
authors: R
authors: Pohlmeyer
authors: Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany;
authors: Isabel
authors: http://orcid.org/0000-0002-2289-459X
authors: I
authors: Wilhelm
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany;
authors: Palash Chandra
authors: http://orcid.org/0000-0003-3295-5859
authors: PC
authors: Maity
authors: Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany; and.
authors: Klaus
authors: K
authors: Rajewsky
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Department of Molecular Immunology, Biology III, Faculty of Biology, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany; michael.reth@bioss.uni-freiburg.de elias.hobeika@uni-ulm.de.
authors: Michael
authors: M
authors: Reth
authors: Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany; Institute of Immunology, University Hospital Ulm, 89081 Ulm, Germany michael.reth@bioss.uni-freiburg.de elias.hobeika@uni-ulm.de.
authors: Elias
authors: E
authors: Hobeika
mesh_terms: D000818:Animals; D053265:B-Cell Activation Factor Receptor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics; D059865:Endoplasmic Reticulum Stress; D015870:Gene Expression; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction
chemical_list: D053265:B-Cell Activation Factor Receptor; C486662:Tnfrsf13c protein, mouse