title: Human regulatory B cells combine phenotypic and genetic hallmarks with a distinct differentiation fate.
abstract: Regulatory B cells (B-reg) produce IL-10 and suppress inflammation in both mice and humans, but limited data on the phenotype and function of these cells have precluded detailed assessment of their contribution to host immunity. In this article, we report that human B-reg cannot be defined based on a phenotype composed of conventional B cell markers, and that IL-10 production can be elicited in both the CD27(+) memory population and naive B cell subset after only a brief stimulation in vitro. We therefore sought to obtain a better definition of IL-10-producing human B-regs using a multiparameter analysis of B cell phenotype, function, and gene expression profile. Exposure to CpG and anti-Ig are the most potent stimuli for IL-10 secretion in human B cells, but microarray analysis revealed that human B cells cotreated with these reagents resulted in only ∼0.7% of genes being differentially expressed between IL-10(+) and IL-10(-) cells. Instead, connectivity map analysis revealed that IL-10-secreting B cells are those undergoing specific differentiation toward a germinal center fate, and we identified a CD11c(+) B cell subset that was not capable of producing IL-10 even under optimal conditions. Our findings will assist in the identification of a broader range of human pro-B-reg populations that may represent novel targets for immunotherapy.
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Wenyu
authors: W
authors: Lin
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Daniela
authors: D
authors: Cerny
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Edmond
authors: E
authors: Chua
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Kaibo
authors: K
authors: Duan
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: June Tai Jing
authors: JT
authors: Yi
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Nurhidaya Binte
authors: NB
authors: Shadan
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Josephine
authors: J
authors: Lum
authors: INSERM U905, Normandie University, 76183 Rouen, France; and Department of Dermatology, Rouen University Hospital, 76183 Rouen, France.
authors: Maud
authors: M
authors: Maho-Vaillant
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Francesca
authors: F
authors: Zolezzi
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Siew Cheng
authors: SC
authors: Wong
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Anis
authors: A
authors: Larbi
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Katja
authors: K
authors: Fink
authors: INSERM U905, Normandie University, 76183 Rouen, France; and Department of Dermatology, Rouen University Hospital, 76183 Rouen, France.
authors: Philippe
authors: P
authors: Musette
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648;
authors: Michael
authors: M
authors: Poidinger
authors: Biomedical Sciences Institutes, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648; INSERM U905, Normandie University, 76183 Rouen, France; and sebastien.calbo@univ-rouen.fr.
authors: Sébastien
authors: S
authors: Calbo
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; C508609:IL10 protein, human; C556062:IL10 protein, mouse; D009838:Oligodeoxyribonucleotides; D016753:Interleukin-10