title: Independent recruitment of Igh alleles in V(D)J recombination.
abstract: How the vast majority of B cells express only one of the two alleles at their immunoglobulin loci remains a biological puzzle. Here, in mice reconstituted with a single haematopoietic stem cell, we demonstrate that each of the two immunoglobulin heavy chain (Igh) alleles has a similar probability to be the first to undergo V(H) to DJ(H) rearrangement. We also observe this similar probability in clones from multipotent and common lymphoid precursors. The extreme biases in the expression of the alleles that we find in more differentiated subsets are mostly due to constraints imposed by early rearrangements. Our data demonstrate that each of the two Igh alleles in a B cell behaves independently of the other, up to the moment when a successful rearrangement in one allele triggers a feedback mechanism that prevents further recombination.
authors.affiliation: Epigenetics and Soma Laboratory, Instituto Gulbenkian de Ciência, Rua da Quinta Grande, n° 6, 2780-156 Oeiras, Portugal.
authors.forename: Clara F
authors.initials: CF
authors.lastname: Alves-Pereira
authors.affiliation: Epigenetics and Soma Laboratory, Instituto Gulbenkian de Ciência, Rua da Quinta Grande, n° 6, 2780-156 Oeiras, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: de Freitas
authors.affiliation: Flow Cytometry Laboratory UIC, Instituto Gulbenkian de Ciência, Rua da Quinta Grande, n° 6, 2780-156 Oeiras, Portugal.
authors.forename: Telma
authors.initials: T
authors.lastname: Lopes
authors.affiliation: Flow Cytometry Laboratory UIC, Instituto Gulbenkian de Ciência, Rua da Quinta Grande, n° 6, 2780-156 Oeiras, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Gardner
authors.affiliation: Epigenetics and Soma Laboratory, Instituto Gulbenkian de Ciência, Rua da Quinta Grande, n° 6, 2780-156 Oeiras, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Marta
authors.affiliation: 1] Unité Lymphopoïèse, Institut Pasteur, 25, Rue du Dr Roux, 75724 Paris, France [2] INSERM U668, F-75015 Paris, France.
authors.forename: Paulo
authors.initials: P
authors.lastname: Vieira
authors.affiliation: Epigenetics and Soma Laboratory, Instituto Gulbenkian de Ciência, Rua da Quinta Grande, n° 6, 2780-156 Oeiras, Portugal.
authors.forename: Vasco M
authors.initials: VM
authors.lastname: Barreto
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002999:Clone Cells; D044127:Epigenesis, Genetic / Q000276:immunology*; D025461:Feedback, Physiological; D005260:Female; D005786:Gene Expression Regulation; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction; D059010:Single-Cell Analysis; D060152:V(D)J Recombination / Q000276:immunology*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region