CD10 delineates a subset of human IL-4 producing follicular helper T cells involved in the survival of follicular lymphoma B cells

Blood. 2015 Apr 9;125(15):2381-5. doi: 10.1182/blood-2015-02-625152. Epub 2015 Mar 2.

Abstract

In follicular lymphoma (FL), follicular helper T cells (TFH) have been depicted as one of the main components of the malignant B-cell niche and a promising therapeutic target. Although defined by their capacity to sustain FL B-cell growth together with specific gene expression and cytokine secretion profiles, FL-TFH constitute a heterogeneous cell population. However, specific markers reflecting such functional heterogeneity are still lacking. In this study, we demonstrate that CD10 identifies a subset of fully functional germinal center TFH in normal secondary lymphoid organs. Importantly, this subset is amplified in the FL context, unlike in other B-cell lymphomas with a follicular growth pattern. Furthermore, whereas FL-TFH produce high levels of interleukin (IL)-21 and low levels of IL-17 irrespectively of their CD10 expression, CD10(pos) FL-TFH specifically exhibit an IL-4(hi)IFN-γ(lo)TNF-α(hi) cytokine profile associated with a high capacity to sustain directly and indirectly malignant B-cell survival. Altogether, our results highlight the important role of this novel functional subset in the FL cell niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • Cell Survival
  • Child
  • Germinal Center / cytology*
  • Germinal Center / immunology
  • Germinal Center / pathology
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / immunology
  • Interleukin-4 / analysis
  • Interleukin-4 / immunology*
  • Lymphoma, Follicular / immunology*
  • Lymphoma, Follicular / pathology
  • Neprilysin / analysis
  • Neprilysin / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma
  • Neprilysin