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

TY - JOUR

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 -