Transgenic hen-egg lysozyme-specific B cells (green) and control, nontransgenic B cells (red) were transferred into syngeneic mice. One day later, the animals were injected with hen-egg lysozyme and one hour later, the inguinal lymph nodes removed and examined. The relocation of the antigen-engaged B cells to the rim of the follicle can be seen most clearly in the xz projection view in (B). (From T. Okada et al., PLoS Biology, 3(6):e150, May 3, 2005.)

Though we think of them as blood cells, lymphocytes spend much of their time in distinct locations in the body. Now teams at three University of California schools have for the first time captured, in vivo, immune cells in motion as they differentiate and respond to antigen within these compartments.

The key technology underlying the two papers: two-photon microscopy. In two-photon microscopy fluorophores are excited simultaneously by two photons of twice the...


In the second article, Cahalan collaborated with Jason Cyster of UC San Francisco, to study the movement of T cells and B cells in lymph nodes after B-cell activation.2 Previous studies showed that before activation, lymphocytes move in a random walk, Cahalan explains. By tracking the behavior of cells in real time following immunization, the authors showed that activated B cells in fact migrate directionally toward the follicle edge along a CCL21 chemokine gradient. "We believe that our work is one of the clearest examples of a chemotactic event occurring in multicellular organisms," says Cyster.

The researchers also tracked interactions between B cells and helper T cells during the initial stages of antigen-induced migration. B cells and T cells are normally found in specific zones in the lymph nodes, but after each cell encounters antigen, they migrate to the edges of their respective zones and interact, initiating an antibody response. During this phase, B cells and T cells formed one-to-one conjugate pairs that appeared to "dance" and exchange partners, with the B cell "leading" the T cell, Cahalan says.

This observation conflicts with a prior study showing that T cells act as leaders.3 Ron Germain of the National Institute of Allergy and Infectious Diseases notes that further experiments will be needed to determine "who's leading the march."

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