title: Role of Polycomb RYBP in Maintaining the B-1-to-B-2 B-Cell Lineage Switch in Adult Hematopoiesis.
abstract: Polycomb chromatin modifiers regulate hematopoietic pluripotent stem and progenitor cell self-renewal and expansion. Polycomb complex redundancy and biochemical heterogeneity complicate the unraveling of the functional contributions of distinct components. We have studied the hematopoietic activity of RYBP, a direct interactor and proposed modulator of RING1A/RING1B-dependent histone H2A monoubiquitylation (H2AUb). Using a mouse model to conditionally inactivate Rybp in adult hematopoiesis, we have found that RYBP deletion results in a reversion of B-1-to-B-2 B-cell progenitor ratios, i.e., of the innate (predominantly fetal) to acquired (mostly adult) immunity precursors. Increased numbers of B-1 progenitors correlated with a loss of pre-proB cells, the B-2 progenitors. RYBP-deficient stem and progenitor cell populations (LKS) and isolated common lymphoid progenitors (CLP) gave rise to increased numbers of B-1 progenitors in vitro. Rybp inactivation, however, did not result in changes of global H2AUb and did not interact genetically with Ring1A or Ring1B deletions. These results show that a sustained regulation of the B-1-to-B-2 switch is needed throughout adult life and that RYBP plays an important role in keeping B-2 dominance, most likely independently of its Polycomb affiliation.
authors.affiliation: Department of Biochemistry, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, IdiPAZ, Madrid, Spain ccales@iib.uam.es mvidal@cib.csic.es.
authors.forename: Carmela
authors.initials: C
authors.lastname: Calés
authors.affiliation: Department of Biochemistry, Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas Alberto Sols CSIC-UAM, IdiPAZ, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Pavón
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Starowicz
authors.affiliation: Anatomy and Histopathology, Facultad de Veterinaria, Universidad de León, León, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pérez
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Bravo
authors.affiliation: Laboratory for Immune Regeneration and Laboratory for Developmental Genetics, IMS RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Ikawa
authors.affiliation: Laboratory for Immune Regeneration and Laboratory for Developmental Genetics, IMS RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain ccales@iib.uam.es mvidal@cib.csic.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vidal
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002460:Cell Line; D019070:Cell Lineage; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D012097:Repressor Proteins; C120616:Rybp protein, mouse; D063150:Polycomb Repressive Complex 1; C489840:Ring1 protein, mouse; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases