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Participation of B‐cell‐activating factor receptors in the pathogenesis of immune thrombocytopenia
Author(s) -
Min Y.N.,
Wang C.Y.,
Li X.X.,
Hou Y.,
Qiu J.H.,
Ma J.,
Shao L.L.,
Zhang X.,
Wang Y.W.,
Peng J.,
Hou M.,
Shi Y.
Publication year - 2016
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13246
Subject(s) - b cell activating factor , receptor , immunology , immune system , biology , microbiology and biotechnology , b cell , antibody , medicine
Essentials Dysfunctional B‐cell‐activating factor (BAFF) system is related to many autoimmune diseases. The regulatory functions of BAFF/BAFF receptors were investigated in an in vitro coculture system. Different regulatory roles of BAFF were investigated via different receptors in immune thrombocytopenia. The upregulated BAFF receptors on autoreactive lymphocytes lead to their hypersensitivity to BAFF.Summary Background The pathogenesis of immune thrombocytopenia ( ITP ) remains enigmatic. B‐cell‐activating factor ( BAFF ) and its receptors ( BAFF receptor [ BAFF ‐R], transmembrane activator and calcium modulator and cyclophilin ligand interactor [ TACI ], and B‐cell maturation antigen) play central roles in the integrated homeostatic regulation of lymphocytes. Objectives To investigate the pathologic roles of BAFF receptors in regulating the bioactivities of lymphocytes in ITP . Methods An in vitro culture system was established by stimulating CD 14 − peripheral lymphocytes with platelet‐preloaded dendritic cells in the presence of recombinant human BAFF (rh BAFF ; 20 ng mL −1 ). The functions of BAFF receptors were specifically blocked with blocking antibodies. Results BAFF ‐R, besides prolonging the survival of B cells in both patients and healthy controls, prominently promoted the survival of CD 8 + T cells and the proliferation of B cells in patients with ITP . TACI , as a positive regulator, not only promoted the proliferation of CD 4 + and CD 8 + T cells, but also significantly enhanced the secretion of interleukin‐4 in patients with ITP , but not in controls. Besides revealing the pathologic roles of BAFF receptors, these results also indicate that lymphocytes of patients with ITP have enhanced antiapoptotic or proliferative capacity as compared with those from healthy controls when exposed under similar stimulation of rh BAFF . Further study demonstrated that activated autoreactive B cells and CD 4 + T cells from patients with ITP showed significantly higher expression of BAFF ‐R or TACI than those from healthy controls. Conclusions Both BAFF ‐R and TACI are pathogenic participants in ITP . Their dysregulated expression in patients with ITP may lead to hyperreactivity of activated autoreactive lymphocytes in response to rh BAFF , and thus is highly significant in the pathogenesis of ITP .