title: A hypomorphic IgH-chain allele affects development of B-cell subsets and favours receptor editing.
abstract: The quality and quantity of BCR signals impact on cell fate decisions of B lymphocytes. Here, we describe novel gene-targeted mice, which in the context of normal VDJ recombination show hypomorphic expression of immunoglobulin μ heavy chain (μHC) mRNA levels and hence lower pre-BCR and BCR levels. Hypomorphic expression of μHC leads to augmented selection processes at all stages of B-cell development, noticeably at the expansion of pre-B cells, the positive selection of immature B lymphocytes in the bone marrow and the selection of the follicular (FO), marginal zone (MZ) and B1 B-lymphocyte compartment in peripheral lymphoid organs. Immature as well as mature FO and MZ B lymphocytes in the peripheral lymphoid organs express lower levels of the receptor for B-cell activating factor (BAFF). In addition, hypomorphic expression of the BCR favours receptor editing. Together, our results highlight the critical importance of pre-BCR and BCR receptor levels for the normal development of B-lymphocyte subpopulations in the context of intact VDJ recombination and a diverse antibody repertoire.
authors.affiliation: Department of Biology, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brenner
authors.forename: Diana
authors.initials: D
authors.lastname: Drewel
authors.forename: Thomas
authors.initials: T
authors.lastname: Steinbart
authors.forename: Florian
authors.initials: F
authors.lastname: Weisel
authors.forename: Eric
authors.initials: E
authors.lastname: Härtel
authors.forename: Sonja
authors.initials: S
authors.lastname: Pötzsch
authors.forename: Heike
authors.initials: H
authors.lastname: Welzel
authors.forename: Andreas
authors.initials: A
authors.lastname: Brandl
authors.forename: Philipp
authors.initials: P
authors.lastname: Yu
authors.forename: Geert C
authors.initials: GC
authors.lastname: Mudde
authors.forename: Astrid
authors.initials: A
authors.lastname: Schweizer
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Winkler
mesh_terms: D000483:Alleles; D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000502:physiology; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics / Q000502:physiology*; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
chemical_list: D053265:B-Cell Activation Factor Receptor; D007148:Immunoglobulin mu-Chains; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C522403:Siglecg protein, mouse