title: Cutting Edge: Redox Signaling Hypersensitivity Distinguishes Human Germinal Center B Cells.
abstract: Differences in the quality of BCR signaling control key steps of B cell maturation and differentiation. Endogenously produced H2O2 is thought to fine tune the level of BCR signaling by reversibly inhibiting phosphatases. However, relatively little is known about how B cells at different stages sense and respond to such redox cues. In this study, we used phospho-specific flow cytometry and high-dimensional mass cytometry (CyTOF) to compare BCR signaling responses in mature human tonsillar B cells undergoing germinal center (GC) reactions. GC B cells, in contrast to mature naive B cells, memory B cells, and plasmablasts, were hypersensitive to a range of H2O2 concentrations and responded by phosphorylating SYK and other membrane-proximal BCR effectors in the absence of BCR engagement. These findings reveal that stage-specific redox responses distinguish human GC B cells.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.|Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Hannah G
authors.initials: HG
authors.lastname: Polikowsky
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Cara E
authors.initials: CE
authors.lastname: Wogsland
authors.affiliation: Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Diggins
authors.affiliation: Centre for Cancer Biomedicine, University of Oslo, Oslo University Hospital, Oslo, Norway.|Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Kanutte
authors.initials: K
authors.lastname: Huse
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.|Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Irish
mesh_terms: D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016130:Immunophenotyping; D010084:Oxidation-Reduction; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011947:Receptors, Antigen, B-Cell; D006861:Hydrogen Peroxide; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6