title: Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response.
abstract: Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cellsin vivo. However, it is unclear whether RA has a direct effect on T-independent B cell responsesin vivo. To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P1in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.
authors.affiliation: Department of Mucosal Immunology, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: Marks
authors.affiliation: Department of Immune Regulation and Intervention, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
authors.forename: Carla
authors.initials: C
authors.lastname: Ortiz
authors.affiliation: Department of Immune Regulation and Intervention, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
authors.forename: Eirini
authors.initials: E
authors.lastname: Pantazi
authors.affiliation: Department of Immune Regulation and Intervention, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
authors.forename: Charlotte S
authors.initials: CS
authors.lastname: Bailey
authors.affiliation: Department of Mucosal Immunology, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Lord
authors.affiliation: Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, The University of Iowa , Iowa City, IA , USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Waldschmidt
authors.affiliation: Department of Immune Regulation and Intervention, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London, London, UK; Department of Microbiology and Immunology of Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH, USA.
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
authors.affiliation: Department of Immune Regulation and Intervention, Division of Transplantation Immunology & Mucosal Biology, Guy's Hospital, King's College London , London , UK.
authors.forename: Raul
authors.initials: R
authors.lastname: Elgueta
keywords: B cell; immunoglobulins; marginal zone; peritoneum; retinoic acid