T follicular helper cells transiently unlock a plasticity state in germinal centre B cells during the humoral immune response

Dec 30, 2025Nature cell biology

Helper T Cells Briefly Allow Flexibility in Germinal Center B Cells During Antibody Responses

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Abstract

GC B cells show enhanced capacity for reprogramming into induced pluripotent stem cells due to unique epigenetic plasticity.

  • GC B cells exhibit transient epigenetic plasticity not seen in other mature B cells.
  • This plasticity is linked to T follicular helper cells and does not result from increased cell division or MYC activation.
  • The weakening of B-cell identity and activation of stem and progenitor programs is driven by NF-κB and signals from T cells.
  • Physiological plasticity in GC B cells is regulated by the affinity maturation process during positive selection.
  • Loss of histone 1, which normally restricts access to embryonic stem cell programs, increases GC B cell plasticity.
  • Patients with B-cell lymphoma showing signs of GC plasticity may have worse clinical outcomes.

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