Naive T cells become activated by recognizing antigen fragments that are bound to MHC complexes on the surface of dendritic cells (DCs). Naive B cells, however, are thought to primarily recognize intact protein antigens that have entered the B-cell-rich follicular area of the lymph node. Because the pattern of flow of lymph through the node means that B cells have restricted access to antigen, Hai Qi, together with his colleagues in Ronald Germain's group, asked whether the activation of B cells might also be assisted by a system of cell-aided antigen delivery. They now report in Science that antigen-bearing DCs can indeed activate lymph-node B cells outside the follicle.

The authors first showed that DC-associated antigen could directly induce B-cell activation in culture. They showed that hen-egg lysozyme that was endocytosed by DCs and presented on the cell surface could activate B cells in vitro. These findings prompted the authors to ask how naive B cells might come into contact with antigen-carrying DCs in vivo, considering that most DCs in the lymph nodes are found in the T-cell zone.

As B cells migrate from the blood to the lymph-node follicles, their first location in the parenchyma is the region surrounding the high endothelial venules (HEVs); this region is also rich in migrating antigen-bearing DCs. Qi et al. reasoned that the region around HEVs, therefore, might be where B cells survey for DC-associated antigens. Indeed, lymph-node sections stained for B cells and to delineate tissue landmarks showed areas of recently arrived B cells concentrated around the HEVs, where they colocalized with and physically contacted DCs. But were these associations resulting in B-cell activation? Using two-photon intravital microscopy, the authors showed that contact with antigen-laden DCs triggered receptor-dependent signalling in B cells in the lymph node shortly after the B cells left the areas around the HEVs, but before they migrated into the follicle.

So, Qi et al. found that B cells enter the lymph node and survey the local antigen-bearing DCs in the areas surrounding the HEVs. B-cell-receptor-mediated acquisition of antigen (which is a hallmark of specific B-cell activation) then occurs by direct B-cell–DC interactions in the T-cell zone, rather than by B cells associating with antigen that is spontaneously released by the DCs. Activated B cells then face temporary arrested migration, which leads to extrafollicular accumulation in the T-cell zone, before completing their migration to the follicle.

The authors suggest that antigen-specific B-cell–DC interactions might have a role in promoting T-cell-dependent antibody responses in vivo. Interestingly, they also propose that by presenting both T- and B-cell epitopes that are derived from the same antigen, DCs could perhaps serve as facilitators of the activation, colocalization and mutual communication of the rare antigen-specific T and B cells that form the basis of our adaptive immune system.