|Title||Dynamic signaling by T follicular helper cells during germinal center B cell selection.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Shulman, iv Z, Gitlin AD, Weinstein JS, Lainez B, Esplugues E, Flavell RA, Craft JE, Nussenzweig MC|
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+).
|Grant List||AI037526-19 / AI / NIAID NIH HHS / United States |
AI072529-06 / AI / NIAID NIH HHS / United States
AI100663-02 / AI / NIAID NIH HHS / United States
AR053495-08 / AR / NIAMS NIH HHS / United States
AR40072-24 / AR / NIAMS NIH HHS / United States
T32GM07739 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
Dynamic signaling by T follicular helper cells during germinal center B cell selection.