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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.
Original language | English |
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Pages (from-to) | 4552-9 |
Number of pages | 8 |
Journal | Blood |
Volume | 120 |
Issue number | 23 |
Early online date | 11 Oct 2012 |
DOIs | |
Publication status | Published - 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
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Dive into the research topics of 'CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines'. Together they form a unique fingerprint.Projects
- 3 Finished
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A Bug in the System: How Does Salmonella Induce Novel B Cell Responses?
27/10/08 → 26/10/11
Project: Research Councils
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Probing the Unexpected Sensitivity of Autoantibody Production to Anti-B Cell Therapy with Rituximab Anti-CD20 Antibody
Savage, C. & MacLennan, I.
12/09/05 → 11/09/08
Project: Research Councils