title: Long-Range Control of V(D)J Recombination & Allelic Exclusion: Modeling Views.
abstract: Allelic exclusion of immunoglobulin (Ig) and T-cell receptor (TCR) genes ensures the development of B and T lymphocytes operating under the mode of clonal selection. This phenomenon associates asynchronous V(D)J recombination events at Ig or TCR alleles and inhibitory feedback control. Despite years of intense research, however, the mechanisms that sustain asymmetric choice in random Ig/TCR dual allele usage and the production of Ig/TCR monoallelic expressing B and T lymphocytes remain unclear and open for debate. In this chapter, we first recapitulate the biological evidence that almost from the start appeared to link V(D)J recombination and allelic exclusion. We review the theoretical models previously proposed to explain this connection. Finally, we introduce our own mathematical modeling views based on how the developmental dynamics of individual lymphoid cells combine to sustain allelic exclusion.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288 Marseille, France.
authors.forename: Pernelle
authors.initials: P
authors.lastname: Outters
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288 Marseille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jaeger
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288 Marseille, France.
authors.forename: Nancy
authors.initials: N
authors.lastname: Zaarour
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, Inserm, U1104, CNRS UMR7280, 13288 Marseille, France. Electronic address: ferrier@ciml.univ-mrs.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ferrier
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D005803:Genes, Immunoglobulin; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D060152:V(D)J Recombination
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: Allelic exclusion; Epigenetics; Immunoglobulin; Mathematical modeling; T-cell receptor; V(D)J recombination