Lymphocyte tracks

Lymphocytes wander around lymph nodes to find their rare target: the dendritic cells that carry an antigen that they recognize. But this apparently random wandering is orchestrated, say Marc Bajénoff, Ronald Germain (NIAID, Bethesda, MD), and colleagues. The cells use a fibroblast network as train tracks to guide them on their travels.

Past experiments using similar intravital microscopy methods have not systematically visualized these train tracks, although lymphocytes were seen to make suspiciously sharp turns. “Lymphocytes have been swimming in an inky void, but that's an artifact of the method,” says Germain. For the first time his colleagues labeled not just the added lymphocytes but also the stromal host cells constituting the backbone of the lymph node.

In both static and live images, T and B cells were seen associated with and crawling along fibroblastic reticular cells (FRCs) in the T cell area. B cells also crossed over and moved along a follicular dendritic cell (FDC) network in the B cell area. Approximately 90% of lymphocyte turns were associated with FRC or FDC fibers running at the corresponding angles.

The networks probably help out in a couple of ways. First, lymphocytes crawling along the networks should more easily meet their target dendritic cells, which are also attached to the networks. Second, the networks are covered with motility-stimulating factors that may help keep the lymphocytes moving. The group hopes to determine the signals that maintain both the movement along and attachment to the networks, and to see whether other cells or signals can divert lymphocytes from their network-determined pathways.

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