Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1182/blood-2014-03-563445

Type

Journal article

Journal

Blood

Publication Date

10/2014

Volume

124

Pages

2858 - 2866

Addresses

Laboratory of Translational Immunology, University Medical Center, Utrecht, The Netherlands; Centre de Recherche INSERM 1098, University of Bourgogne/Franche-Comté, Fédération Hospitalo-Universitaire Integrated Center for Research in Inflammatory Diseases, Bourgogne, France; Department of Internal Medicine and Clinical Immunology, Competence Center for Autoimmune Cytopenia, University Hospital, Dijon, France;

Keywords

Germinal Center, Spleen, B-Lymphocytes, B-Lymphocyte Subsets, Plasma Cells, Blood Platelets, T-Lymphocytes, Helper-Inducer, Humans, Purpura, Thrombocytopenic, Idiopathic, Immunoglobulin G, CD40 Ligand, RNA, Messenger, Antigens, CD, Interleukins, Lymphocyte Count, Cell Differentiation, Cell Proliferation, Antibody Formation, Phenotype, Adult, Aged, Middle Aged, Female, Male