CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines.
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.
Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom. karine@kserre.net
Karine
K
Serre
Adam F
AF
Cunningham
Ruth E
RE
Coughlan
Andreia C
AC
Lino
Antal
A
Rot
Elin
E
Hub
Katrin
K
Moser
Rudolf
R
Manz
Alastair
A
Ferraro
Roger
R
Bird
Kai-Michael
KM
Toellner
Jocelyne
J
Demengeot
Ian C M
IC
MacLennan
Elodie
E
Mohr
D019264:Adoptive Transfer; D000534:Alum Compounds; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D014612:Vaccines / Q000276:immunology*; D000098815:T-bet Transcription Factor
D000534:Alum Compounds; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C515188:Cxcr3 protein, mouse; D008024:Ligands; D054367:Receptors, CXCR3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014612:Vaccines; C446402:ovalbumin-alum; D007371:Interferon-gamma; D010047:Ovalbumin