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

Research output: Contribution to journalArticle

Authors

Abstract

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.

Details

Original languageEnglish
Pages (from-to)4552-9
Number of pages8
JournalBlood
Volume120
Issue number23
Early online date11 Oct 2012
Publication statusPublished - 29 Nov 2012

Keywords

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