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.
MeSH terms
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Adoptive Transfer
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Alum Compounds
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / transplantation
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / transplantation
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Cell Differentiation / immunology
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Cell Movement / immunology*
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Chemokine CXCL10 / immunology
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Chemokine CXCL10 / metabolism
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Flow Cytometry
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Germinal Center / immunology
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Germinal Center / metabolism
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Immunization / methods
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Ligands
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Mice
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Mice, Inbred C57BL
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Ovalbumin / immunology
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Receptors, CXCR3 / genetics
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Receptors, CXCR3 / immunology*
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Receptors, CXCR3 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / immunology*
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T-Box Domain Proteins / metabolism
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Up-Regulation / genetics
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Vaccines / immunology*
Substances
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Alum Compounds
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Chemokine CXCL10
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Cxcl10 protein, mouse
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Cxcr3 protein, mouse
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Ligands
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Receptors, CXCR3
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Vaccines
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ovalbumin-alum
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Interferon-gamma
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Ovalbumin