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

Karine Serre; Adam F Cunningham; Ruth E Coughlan; Andreia C Lino; Antal Rot; Elin Hub; Katrin Moser; Rudolf Manz; Alastair Ferraro; Roger Bird; Kai-Michael Toellner; Jocelyne Demengeot; Ian C M MacLennan; Elodie Mohr

doi:10.1182/blood-2012-03-417733

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

Karine Serre, Adam F Cunningham, Ruth E Coughlan, Andreia C Lino, Antal Rot, Elin Hub, Katrin Moser, Rudolf Manz, Alastair Ferraro, Roger Bird, Kai-Michael Toellner, Jocelyne Demengeot, Ian C M MacLennan, Elodie Mohr

Research output: Contribution to journal › Article › peer-review

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
Pages (from-to)	4552-4559
Journal	Blood
Volume	120
Issue number	23
DOIs	https://doi.org/10.1182/blood-2012-03-417733
Publication status	Published - 29 Nov 2012

Keywords

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

Access to Document

10.1182/blood-2012-03-417733

http://www.bloodjournal.org/content/120/23/4552?sso-checked=true

Cite this

Serre, K., Cunningham, A. F., Coughlan, R. E., Lino, A. C., Rot, A., Hub, E., Moser, K., Manz, R., Ferraro, A., Bird, R., Toellner, K.-M., Demengeot, J., MacLennan, I. C. M., & Mohr, E. (2012). CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines. Blood, 120(23), 4552-4559. https://doi.org/10.1182/blood-2012-03-417733

@article{9228be3488f54ad3b74e17bdba7724e3,

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

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.",

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

author = "Karine Serre and Cunningham, {Adam F} and Coughlan, {Ruth E} and Lino, {Andreia C} and Antal Rot and Elin Hub and Katrin Moser and Rudolf Manz and Alastair Ferraro and Roger Bird and Kai-Michael Toellner and Jocelyne Demengeot and MacLennan, {Ian C M} and Elodie Mohr",

year = "2012",

month = nov,

day = "29",

doi = "10.1182/blood-2012-03-417733",

language = "English",

volume = "120",

pages = "4552--4559",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

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Serre, K, Cunningham, AF, Coughlan, RE, Lino, AC, Rot, A, Hub, E, Moser, K, Manz, R, Ferraro, A, Bird, R, Toellner, K-M, Demengeot, J, MacLennan, ICM & Mohr, E 2012, 'CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines', Blood, vol. 120, no. 23, pp. 4552-4559. https://doi.org/10.1182/blood-2012-03-417733

TY - JOUR

T1 - CD8 T cells induce T-bet-dependent migration toward CXCR3 ligands by differentiated B cells produced during responses to alum-protein vaccines

AU - Serre, Karine

AU - Cunningham, Adam F

AU - Coughlan, Ruth E

AU - Lino, Andreia C

AU - Rot, Antal

AU - Hub, Elin

AU - Moser, Katrin

AU - Manz, Rudolf

AU - Ferraro, Alastair

AU - Bird, Roger

AU - Toellner, Kai-Michael

AU - Demengeot, Jocelyne

AU - MacLennan, Ian C M

AU - Mohr, Elodie

PY - 2012/11/29

Y1 - 2012/11/29

N2 - 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.

AB - 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.

KW - Adoptive Transfer

KW - Alum Compounds

KW - Animals

KW - B-Lymphocytes

KW - CD4-Positive T-Lymphocytes

KW - CD8-Positive T-Lymphocytes

KW - Cell Differentiation

KW - Cell Movement

KW - Chemokine CXCL10

KW - Flow Cytometry

KW - Germinal Center

KW - Immunization

KW - Interferon-gamma

KW - Ligands

KW - Mice

KW - Mice, Inbred C57BL

KW - Ovalbumin

KW - Receptors, CXCR3

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - T-Box Domain Proteins

KW - Th2 Cells

KW - Up-Regulation

KW - Vaccines

U2 - 10.1182/blood-2012-03-417733

DO - 10.1182/blood-2012-03-417733

M3 - Article

C2 - 23065152

SN - 0006-4971

VL - 120

SP - 4552

EP - 4559

JO - Blood

JF - Blood

IS - 23

ER -