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T Cell Accumulation in B Cell Follicles Is Regulated by Dendritic Cells and Is Independent of B Cell Activation

Simon Fillatreau and David Gray

Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom

Address correspondence to David Gray, Institute of Cell, Animal and Population Biology, University of Edinburgh, Ashworth Laboratories, King's Buildings, West Mains Road, Edinburgh EH9 3JT, United Kingdom. Phone: 44-131-650-5500; Fax: 44-131-650-7322; E-mail: d.gray{at}ed.ac.uk

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.

Key Words: T lymphocyte migration • B lymphocytes • OX40 • CXCR5 • lymphoid follicles

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