T cell accumulation in B cell follicles is regulated by dendritic cells and is independent of B cell activation.
We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40(+) DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L-huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.
Fillatreau
Simon
S
Institute of Cell, Animal and Population Biology, University of Edinburgh, Ashworth Laboratories, King's Buildings, West Mains Road, Edinburgh EH9 3JT, Scotland, UK.
Gray
David
D
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D004140:Dinitrophenols / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053278:OX40 Ligand; D010047:Ovalbumin / Q000276:immunology; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D048069:Tumor Necrosis Factors
D019013:CD40 Antigens; C513179:CXCR5 protein, mouse; D004140:Dinitrophenols; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; C045521:dinitrophenol-ovalbumin; D023201:CD40 Ligand; D010047:Ovalbumin