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Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
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BCL6 controls contact-dependent help delivery during follicular T-B cell interactions

Dan Liu1, Jiacong Yan2, Jiahui Sun1

  • 1Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing 100084, China; Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.

Immunity
|August 31, 2021
PubMed

Insights

BCL6 is crucial for follicular helper T (Tfh) cell development and germinal center (GC) formation. This study reveals BCL6 regulates Tfh cell signaling and B cell interactions, essential for GC maintenance.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Follicular helper T (Tfh) cells are essential for germinal center (GC) formation and antibody responses.
  • BCL6 is a known master regulator of Tfh cell differentiation, but its precise functions in GC formation remain incompletely understood.

Purpose of the Study:

  • To elucidate the unique functions of BCL6 in T cells that are essential for germinal center formation.
  • To investigate how BCL6 deficiency impacts Tfh cell function and interactions with B cells.

Main Methods:

  • Conditional knockout mouse models to ablate BCL6 alleles in T cells.
  • Flow cytometry to analyze Tfh cell populations and activation markers.
  • In vivo imaging to assess T cell-B cell interactions and CD40L delivery.

Main Results:

  • BCL6 haploinsufficiency impaired GC formation and Tfh cell maintenance without affecting early T cell activation or localization.
  • BCL6 was found to regulate Tfh cell calcium signaling and CD40L delivery to B cells.
  • Overexpression of CD40L rescued GC formation and Tfh cell maintenance defects in BCL6-haploinsufficient mice.

Conclusions:

  • BCL6 plays critical roles in Tfh cell signaling and B cell interactions, which are essential for GC formation.
  • BCL6 maintains Tfh cell phenotypes in a non-autonomous manner, highlighting its importance beyond T cell intrinsic functions.

Keywords:
BCL6CD40LT-B interactionsTfh cellscalcium signalingfolliclegerminal centerintravital imaginglymph nodestim1

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