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

Z Shulman, AD Gitlin, JS Weinstein, B Lainez… - Science, 2014 - science.org
Science, 2014science.org
T follicular helper (TFH) 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 TFH 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 TFH intracellular free calcium (Ca2+) that were associated with TFH cell …
T follicular helper (TFH) 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 TFH 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 TFH intracellular free calcium (Ca2+) that were associated with TFH cell coexpression of the cytokines interleukin-4 and -21. However, increased intracellular Ca2+ did not arrest TFH cell migration. Instead, TFH 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 Ca2+.
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