Cutting Edge: Redox Signaling Hypersensitivity Distinguishes Human Germinal Center B Cells

J Immunol. 2015 Aug 15;195(4):1364-1367. doi: 10.4049/jimmunol.1500904. Epub 2015 Jul 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Differentiation
  • Gene Expression
  • Germinal Center / immunology*
  • Germinal Center / metabolism*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Immunophenotyping
  • Oxidation-Reduction*
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • Phenotype
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction*

Substances

  • Receptors, Antigen, B-Cell
  • Hydrogen Peroxide
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6