Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help
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Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help. / Hardtke, Svenja; Ohl, Lars; Förster, Reinhold.
in: BLOOD, Jahrgang 106, Nr. 6, 15.09.2005, S. 1924-31.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help
AU - Hardtke, Svenja
AU - Ohl, Lars
AU - Förster, Reinhold
PY - 2005/9/15
Y1 - 2005/9/15
N2 - The production of high-affinity antibodies to T-dependent antigens requires the interaction of B cells and T helper cells expressing receptors specific for the same antigen. Although several mechanisms have been elucidated that regulate B-cell trafficking within lymphoid organs, less is known about molecular cues that guide the small subpopulation of CD4+ follicular T helper cells to B-cell follicles. Using adoptive transfer of transgenic T cells in mice, we demonstrate that antigen-induced activation leads to a finely tuned positioning of T cells either to the T-cell area or the B-cell follicle. We show that expression of CXCR5 is indispensable for T cells to enter B-cell follicles, whereas expression of CCR7 provides a counteracting signal to retain activated T cells in the T-cell area. Although only few T cells transiently migrate from the T-cell area to the B-cell follicle of peripheral lymph nodes following antigenic challenge, this step is essential to provide the help B cells require to produce antibodies efficiently. Thus, we demonstrate that the balanced expression of CCR7 and CXCR5 determines the positioning and proper function of follicular T helper cells.
AB - The production of high-affinity antibodies to T-dependent antigens requires the interaction of B cells and T helper cells expressing receptors specific for the same antigen. Although several mechanisms have been elucidated that regulate B-cell trafficking within lymphoid organs, less is known about molecular cues that guide the small subpopulation of CD4+ follicular T helper cells to B-cell follicles. Using adoptive transfer of transgenic T cells in mice, we demonstrate that antigen-induced activation leads to a finely tuned positioning of T cells either to the T-cell area or the B-cell follicle. We show that expression of CXCR5 is indispensable for T cells to enter B-cell follicles, whereas expression of CCR7 provides a counteracting signal to retain activated T cells in the T-cell area. Although only few T cells transiently migrate from the T-cell area to the B-cell follicle of peripheral lymph nodes following antigenic challenge, this step is essential to provide the help B cells require to produce antibodies efficiently. Thus, we demonstrate that the balanced expression of CCR7 and CXCR5 determines the positioning and proper function of follicular T helper cells.
KW - Adoptive Transfer
KW - Animals
KW - Antibody Formation/immunology
KW - B-Lymphocytes/immunology
KW - Cell Communication/immunology
KW - Chemotaxis, Leukocyte
KW - Germinal Center/immunology
KW - Hemostasis/immunology
KW - Lymphocyte Activation
KW - Mice
KW - Mice, Knockout
KW - Receptors, CCR7
KW - Receptors, CXCR5
KW - Receptors, Chemokine/genetics
KW - Receptors, Cytokine/genetics
KW - T-Lymphocytes/transplantation
KW - T-Lymphocytes, Helper-Inducer/immunology
U2 - 10.1182/blood-2004-11-4494
DO - 10.1182/blood-2004-11-4494
M3 - SCORING: Journal article
C2 - 15899919
VL - 106
SP - 1924
EP - 1931
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 6
ER -