CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines

Blood. 2012 Nov 29;120(23):4552-9. doi: 10.1182/blood-2012-03-417733. Epub 2012 Oct 11.


Antibody-forming cells (AFCs) expressing the chemokine receptor CXCR3 are recruited to sites of inflammation where they help clear pathogens but may participate in autoimmune diseases. Here we identify a mechanism that induces CXCR3 expression by AFC and germinal center (GC) B cells. This happens when CD8 T cells are recruited into CD4 T cell-dependent B-cell responses. Ovalbumin-specific CD4 T cells (OTII) were transferred alone or with ovalbumin-specific CD8 T cells (OTI) and the response to subcutaneous alum-precipitated ovalbumin was followed in the draining lymph nodes. OTII cells alone induce T helper 2-associated class switching to IgG1, but few AFC or GC B cells express CXCR3. By contrast, OTI-derived IFN-γ induces most responding GC B cells and AFCs to express high levels of CXCR3, and diverse switching to IgG2a, IgG2b, with some IgG1. Up-regulation of CXCR3 by GC B cells and AFCs and their migration toward its ligand CXCL10 are shown to depend on B cells' intrinsic T-bet, a transcription factor downstream of the IFN-γR signaling. This model clarifies how precursors of long-lived AFCs and memory B cells acquire CXCR3 that causes their migration to inflammatory foci.

MeSH terms

  • Adoptive Transfer
  • Alum Compounds
  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / transplantation
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Differentiation / immunology
  • Cell Movement / immunology*
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL10 / metabolism
  • Flow Cytometry
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Immunization / methods
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology*
  • Receptors, CXCR3 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*
  • T-Box Domain Proteins / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Up-Regulation / genetics
  • Vaccines / immunology*


  • Alum Compounds
  • Chemokine CXCL10
  • Cxcl10 protein, mouse
  • Cxcr3 protein, mouse
  • Ligands
  • Receptors, CXCR3
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Vaccines
  • ovalbumin-alum
  • Interferon-gamma
  • Ovalbumin