scholarly journals T Follicular Helper Cell Dynamics in Germinal Centers

Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 673-677 ◽  
Author(s):  
Ziv Shulman ◽  
Alexander D. Gitlin ◽  
Sasha Targ ◽  
Mila Jankovic ◽  
Giulia Pasqual ◽  
...  
Keyword(s):  
B Cells ◽  
Antigenic Variation ◽  
Germinal Centers ◽  
Cell Dynamics ◽  
Fluorescent Reporter ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Follicular Helper ◽  
T Cell Help ◽  
Dynamic Exchange

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.

scholarly journals Landscape of T Follicular Helper Cell Dynamics in Human Germinal Centers

2020 ◽  
Vol 205 (5) ◽  
pp. 1248-1255
Author(s):  
Emmanuel Donnadieu ◽  
Kerstin Bianca Reisinger ◽  
Sonja Scharf ◽  
Yvonne Michel ◽  
Julia Bein ◽  
...  
Keyword(s):  
Germinal Centers ◽  
Helper Cell ◽  
Cell Dynamics ◽  
Follicular Helper ◽  
T Follicular Helper Cell

Chapter 16 Two‐Photon Microscopy and Multidimensional Analysis of Cell Dynamics

2009 ◽  
pp. 349-378 ◽  
Author(s):  
Bernd H. Zinselmeyer ◽  
John Dempster ◽  
David L. Wokosin ◽  
Jonathan J. Cannon ◽  
Robert Pless ◽  
...  
Keyword(s):  
Multidimensional Analysis ◽  
Cell Dynamics ◽  
Two Photon Microscopy ◽  
Two Photon

scholarly journals A distinct subpopulation of CD25− T-follicular regulatory cells localizes in the germinal centers

2017 ◽  
Vol 114 (31) ◽  
pp. E6400-E6409 ◽  
Author(s):  
James Badger Wing ◽  
Yohko Kitagawa ◽  
Michela Locci ◽  
Hannah Hume ◽  
Christopher Tay ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Germinal Center ◽  
Germinal Centers ◽  
Regulatory Cells ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Distinct Subpopulation ◽  
Wide Range ◽  
Multistep Process

T-follicular helper (Tfh) cells differentiate through a multistep process, culminating in germinal center (GC) localized GC-Tfh cells that provide support to GC-B cells. T-follicular regulatory (Tfr) cells have critical roles in the control of Tfh cells and GC formation. Although Tfh-cell differentiation is inhibited by IL-2, regulatory T (Treg) cell differentiation and survival depend on it. Here, we describe a CD25− subpopulation within both murine and human PD1+CXCR5+Foxp3+ Tfr cells. It is preferentially located in the GC and can be clearly differentiated from CD25+ non–GC-Tfr, Tfh, and effector Treg (eTreg) cells by the expression of a wide range of molecules. In comparison to CD25+ Tfr and eTreg cells, CD25− Tfr cells partially down-regulate IL-2–dependent canonical Treg features, but retain suppressive function, while simultaneously up-regulating genes associated with Tfh and GC-Tfh cells. We suggest that, similar to Tfh cells, Tfr cells follow a differentiation pathway generating a mature GC-localized subpopulation, CD25− Tfr cells.

scholarly journals Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers

Blood ◽  
2014 ◽  
Vol 124 (17) ◽  
pp. 2666-2674 ◽  
Author(s):  
Elizabeth F. Wallin ◽  
Elaine C. Jolly ◽  
Ondřej Suchánek ◽  
J. Andrew Bradley ◽  
Marion Espéli ◽  
...  
Keyword(s):  
B Cells ◽  
Germinal Centers ◽  
Treatment Results ◽  
Regulatory Cell ◽  
Follicular Helper ◽  
Key Points ◽  
Cell Maintenance

Key Points RTX treatment results in loss of human GC B cells. Human Tfh and Tfr cells do not require GC B cells for their maintenance.

scholarly journals BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms

2015 ◽  
Vol 212 (4) ◽  
pp. 539-553 ◽  
Author(s):  
Katerina Hatzi ◽  
J. Philip Nance ◽  
Mark A. Kroenke ◽  
Marcella Bothwell ◽  
Elias K. Haddad ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Tcr Signaling ◽  
Cell Fates ◽  
Binding Motifs ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Distinct Cell ◽  
T Cell Help ◽  
External Stimuli

Follicular helper T cells (Tfh cells) are required for T cell help to B cells, and BCL6 is the defining transcription factor of Tfh cells. However, the functions of BCL6 in Tfh cells have largely remained unclear. Here we defined the BCL6 cistrome in primary human germinal center Tfh cells to assess mechanisms of BCL6 regulation of CD4 T cells, comparing and contrasting BCL6 function in T and B cells. BCL6 primarily acts as a repressor in Tfh cells, and BCL6 binding was associated with control of Tfh cell migration and repression of alternative cell fates. Interestingly, although some BCL6-bound genes possessed BCL6 DNA–binding motifs, many BCL6-bound loci were instead characterized by the presence of DNA motifs for AP1 or STAT. AP1 complexes are key positive downstream mediators of TCR signaling and external stimuli. We show that BCL6 can directly bind AP1, and BCL6 depends on AP1 for recruitment to BCL6-binding sites with AP1 motifs, suggesting that BCL6 subverts AP1 activity. These findings reveal that BCL6 has broad and multifaceted effects on Tfh biology and provide insight into how this master regulator mediates distinct cell context–dependent phenotypes.

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