Characterization of a transitional preplasmablast population in the process of human B cell to plasma cell differentiation

• Published in: The Journal of immunology (1950) 2011-10, Vol.187 (8), p.3931-3941
• Main Authors: Jourdan, Michel, Caraux, Anouk, Caron, Gersende, Robert, Nicolas, Fiol, Geneviève, Rème, Thierry, Bolloré, Karine, Vendrell, Jean-Pierre, Le Gallou, Simon, Mourcin, Frédéric, De Vos, John, Kassambara, Alboukadel, Duperray, Christophe, Hose, Dirk, Fest, Thierry, Tarte, Karin, Klein, Bernard
• Format: Article
• Language: English
• Subjects: B-Lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Cell Differentiation; Cell Differentiation - immunology; Enzyme-Linked Immunosorbent Assay; Humans; Immunology; Immunophenotyping; Life Sciences; Oligonucleotide Array Sequence Analysis; Plasma Cells; Plasma Cells - cytology; Plasma Cells - immunology; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1101230

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.