Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia

Blood. 2014 Oct 30;124(18):2858-66. doi: 10.1182/blood-2014-03-563445. Epub 2014 Sep 16.


Antiplatelet-antibody-producing B cells play a key role in immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand (CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibody Formation / drug effects
  • Antibody Formation / immunology*
  • Antigens, CD / metabolism
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • Blood Platelets / drug effects
  • Blood Platelets / immunology*
  • CD40 Ligand / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology*
  • Cell Proliferation / drug effects
  • Female
  • Germinal Center / pathology
  • Humans
  • Immunoglobulin G / biosynthesis
  • Interleukins / pharmacology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Phenotype
  • Plasma Cells / drug effects
  • Plasma Cells / metabolism
  • Plasma Cells / pathology
  • Purpura, Thrombocytopenic, Idiopathic / immunology*
  • Purpura, Thrombocytopenic, Idiopathic / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Spleen / pathology*
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology


  • Antigens, CD
  • Immunoglobulin G
  • Interleukins
  • RNA, Messenger
  • CD40 Ligand
  • interleukin-21