Cutting edge: An in vivo reporter reveals active B cell receptor signaling in the germinal center

J Immunol. 2015 Apr 1;194(7):2993-7. doi: 10.4049/jimmunol.1403086. Epub 2015 Feb 27.

Abstract

Long-lasting Ab responses rely on the germinal center (GC), where B cells bearing high-affinity Ag receptors are selected from a randomly mutated pool to populate the memory and plasma cell compartments. Signaling downstream of the BCR is dampened in GC B cells, raising the possibility that Ag presentation and competition for T cell help, rather than Ag-dependent signaling per se, drive these critical selection events. In this study we use an in vivo reporter of BCR signaling, Nur77-eGFP, to demonstrate that although BCR signaling is reduced among GC B cells, a small population of cells exhibiting GC light zone phenotype (site of Ag and follicular helper T cell encounter) express much higher levels of GFP. We show that these cells exhibit somatic hypermutation, gene expression characteristic of signaling and selection, and undergo BCR signaling in vivo.

Publication types

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

MeSH terms

  • Animals
  • Antigens / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Gene Expression
  • Gene Expression Profiling
  • Genes, Reporter
  • Germinal Center / immunology*
  • Germinal Center / metabolism*
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Transgenic
  • Phenotype
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Receptors, Antigen, B-Cell / metabolism*
  • Signal Transduction*
  • Somatic Hypermutation, Immunoglobulin
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Transcriptome

Substances

  • Antigens
  • Receptors, Antigen, B-Cell