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Dynamic signaling by T follicular helper cells during germinal center B cell selection

2014; American Association for the Advancement of Science; Volume: 345; Issue: 6200 Linguagem: Inglês

10.1126/science.1257861

1095-9203

Ziv Shulman, Alexander D. Gitlin, Jason S. Weinstein, Begoña Lainez, Enric Esplugues, Richard A. Flavell, Joseph Craft, Michel C. Nussenzweig,

Immunotherapy and Immune Responses

T follicular helper (T(FH)) cells select high-affinity, antibody-producing B cells for clonal expansion in germinal centers (GCs), but the nature of their interaction is not well defined. Using intravital imaging, we found that selection is mediated by large but transient contacts between T(FH) and GC B cells presenting the highest levels of cognate peptide bound to major histocompatibility complex II. These interactions elicited transient and sustained increases in T(FH) intracellular free calcium (Ca(2+)) that were associated with T(FH) cell coexpression of the cytokines interleukin-4 and -21. However, increased intracellular Ca(2+) did not arrest TFH cell migration. Instead, T(FH) cells remained motile and continually scanned the surface of many GC B cells, forming short-lived contacts that induced selection through further repeated transient elevations in intracellular Ca(2+).