title: Characterization of a transitional preplasmablast population in the process of human B cell to plasma cell differentiation.
abstract: The early steps of differentiation of human B cells into plasma cells are poorly known. We report a transitional population of CD20(low/-)CD38(-) preplasmablasts along differentiation of human memory B cells into plasma cells in vitro. Preplasmablasts lack documented B cell or plasma cell (CD20, CD38, and CD138) markers, express CD30 and IL-6R, and secrete Igs at a weaker level than do plasmablasts or plasma cells. These preplasmablasts further differentiate into CD20(-)CD38(high)CD138(-) plasmablasts and then CD20(-)CD38(high)CD138(+) plasma cells. Preplasmablasts were fully characterized in terms of whole genome transcriptome profiling and phenotype. Preplasmablasts coexpress B and plasma cell transcription factors, but at a reduced level compared with B cells, plasmablasts, or plasma cells. They express the unspliced form of XBP1 mRNA mainly, whereas plasmablasts and plasma cells express essentially the spliced form. An in vivo counterpart (CD19(+)CD20(low/-)CD38(-)IL-6R(+) cells) of in vitro-generated preplasmablasts could be detected in human lymph nodes (0.06% of CD19(+) cells) and tonsils (0.05% of CD19(+) cells). An open access "B to Plasma Cell Atlas," which makes it possible to interrogate gene expression in the process of B cell to plasma cell differentiation, is provided. Taken together, our findings show the existence of a transitional preplasmablast population using an in vitro model of plasma cell generation and of its in vivo counterpart in various lymphoid tissues.
authors.affiliation: INSERM, Unité 1040, 34000 Montpellier, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Jourdan
authors.forename: Anouk
authors.initials: A
authors.lastname: Caraux
authors.forename: Gersende
authors.initials: G
authors.lastname: Caron
authors.forename: Nicolas
authors.initials: N
authors.lastname: Robert
authors.forename: Geneviève
authors.initials: G
authors.lastname: Fiol
authors.forename: Thierry
authors.initials: T
authors.lastname: Rème
authors.forename: Karine
authors.initials: K
authors.lastname: Bolloré
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vendrell
authors.forename: Simon
authors.initials: S
authors.lastname: Le Gallou
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mourcin
authors.forename: John
authors.initials: J
authors.lastname: De Vos
authors.forename: Alboukadel
authors.initials: A
authors.lastname: Kassambara
authors.forename: Christophe
authors.initials: C
authors.lastname: Duperray
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Thierry
authors.initials: T
authors.lastname: Fest
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016130:Immunophenotyping; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction