Human tonsil B-cell lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell help outside germinal centers

Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):E488-97. doi: 10.1073/pnas.1100898108. Epub 2011 Aug 1.

Abstract

T follicular helper (Tfh) cells represent a Th subset engaged in the help of B-cell responses in germinal centers (GCs). Tfh cells abundantly express the transcription repressor B-cell lymphoma 6 (Bcl6), a factor that is necessary and sufficient for their development in vivo. Whether Tfh or Tfh-committed cells are involved in the help of B cells outside GCs remains unclear, particularly in humans. In this study, we identified a previously undefined BCL6-expressing CD4(+) T-cell subset in human tonsils. This subset expressed IL-7 receptor and chemokine receptor 5 (CXCR5) and inducible costimulator (ICOS) at low levels (CXCR5(lo)ICOS(lo)), and it was found exclusively outside GCs. CXCR5(lo)ICOS(lo) CD4(+) T cells secreted larger amounts of IL-21 and IL-10 than CXCR5(hi)ICOS(hi) GC-Tfh cells upon activation, and they induced proliferation and differentiation of naïve B cells into Ig-producing cells more efficiently than GC-Tfh cells. However, this subset lacked the capacity to help GC-B cells because of the induction of apoptosis of GC-B cells through the FAS/FAS-ligand interaction. CXCR5(lo)ICOS(lo) CD4(+) T cells expressed equivalent amounts of BCL6 transcript with CXCR5(hi)ICOS(hi) GC-Tfh cells, but they expressed less Bcl6 protein. Collectively, our study indicates that CXCR5(lo)ICOS(lo) CD4(+) T cells in human tonsils represent Tfh lineage-committed cells that provide help to naïve and memory B cells outside GCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • CD4-Positive T-Lymphocytes / pathology*
  • Cell Lineage / immunology
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • Germinal Center / immunology*
  • Humans
  • Interleukin-7
  • Lymphoma, B-Cell / pathology*
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger / analysis
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology*
  • Tonsillar Neoplasms / pathology*

Substances

  • BCL6 protein, human
  • DNA-Binding Proteins
  • Interleukin-7
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger