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.
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.
Hardtke
Svenja
S
Institute of Immunology, Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany.
Ohl
Lars
L
Förster
Reinhold
R
D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D018858:Germinal Center / Q000276:immunology*; D006487:Hemostasis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology*
C513179:CXCR5 protein, mouse; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine