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T Follicular Helper Cell Dynamics in Germinal Centers

Science  09 Aug 2013:
Vol. 341, Issue 6146, pp. 673-677
DOI: 10.1126/science.1241680

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Germinal centers are specialized structures within lymph nodes, where B cells undergo the changes required to produce high-affinity antibodies. This process relies on T follicular helper (Tfh) cells. The dynamic properties of Tfh cells and how they affect the selection of B cells, however, are not well understood. Using two-photon laser scanning microscopy of mouse lymph nodes, Shulman et al. (p. 673, published online 25 July) find that Tfh cells are not restricted to a single germinal center, but instead emigrate into neighboring germinal centers within the same lymph nodes. Furthermore, newly activated T cells can enter already established germinal centers and presumably influence ongoing B cell selection and differentiation. Such active movement may ensure maximal diversification of the B cell response and promote the production of high-affinity antibodies.

Abstract

T follicular helper (TFH) cells are a specialized subset of effector T cells that provide help to and thereby select high-affinity B cells in germinal centers (GCs). To examine the dynamic behavior of TFH cells in GCs in mice, we used two-photon microscopy in combination with a photoactivatable fluorescent reporter. Unlike GC B cells, which are clonally restricted, TFH cells distributed among all GCs in lymph nodes and continually emigrated into the follicle and neighboring GCs. Moreover, newly activated TFH cells invaded preexisting GCs, where they contributed to B cell selection and plasmablast differentiation. Our data suggest that the dynamic exchange of TFH cells between GCs ensures maximal diversification of T cell help and that their ability to enter ongoing GCs accommodates antigenic variation during the immune response.

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