title: Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo.
abstract: Regulatory B cells that are functionally defined by their capacity to express IL-10 (B10 cells) downregulate inflammation and autoimmunity. In studies using well-defined IL-10 reporter mice, this rare B10 cell subset was also found to maintain a capacity for plasma cell differentiation. During a transient period of il10 transcription, the blimp1 and irf4 transcription factors were induced in B10 cells, whereas pax5 and bcl6 were downregulated as a significant fraction of B10 cells completed the genetic and phenotypic program leading to Ab-secreting cell differentiation in vitro and in vivo. B10 cell-derived IgM reacted with both self- and foreign Ags, whereas B10 cells generated Ag-specific IgG in response to immunizations. Moreover, B10 cells represented a significant source of serum IgM and IgG during adoptive-transfer experiments and produced Ag-specific, polyreactive and autoreactive Ab specificities that were consistent with their expression of a diverse AgR repertoire. Thereby, B10 cells limit inflammation and immune responses by the transient production of IL-10, and may facilitate clearance of their eliciting Ags through an inherent capacity to quickly generate polyreactive and/or Ag-specific Abs during humoral immune responses.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Damian
authors.initials: D
authors.lastname: Maseda
authors.forename: Susan H
authors.initials: SH
authors.lastname: Smith
authors.forename: David J
authors.initials: DJ
authors.lastname: DiLillo
authors.forename: Jacquelyn M
authors.initials: JM
authors.lastname: Bryant
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Candando
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology*; D000941:Antigens; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D005786:Gene Expression Regulation; D056724:Immunity, Humoral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice
chemical_list: D000941:Antigens; C556062:IL10 protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016753:Interleukin-10