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B cell activation through CD 40 and IL 4R ligation modulates the response of chronic lymphocytic leukaemia cells to BAFF and APRIL
Author(s) -
Ferrer Gerardo,
Bosch Rosa,
Hodgson Kate,
Tejero Rut,
Roué Gael,
Colomer Dolors,
Montserrat Emili,
Moreno Carol
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12645
Subject(s) - b cell activating factor , cd40 , ighv@ , receptor , breakpoint cluster region , chronic lymphocytic leukemia , cancer research , b cell , immunology , biology , medicine , antibody , leukemia , cytotoxic t cell , in vitro , biochemistry
Summary The two tumour necrosis factor family proteins BAFF ( TNFSF 13B) and APRIL ( TNFSF 13) and their receptors [ BAFF ‐R ( TNFRSF 13C), TACI ( TNFRSF 13B), BCMA ( TNFRSF 17)] play a critical role in the survival of normal B cells. The sensitivity of normal B cells to BAFF and APRIL can be modulated by signals regulated by their receptors. This modulation, however, has not been extensively investigated in chronic lymphocytic leukaemia ( CLL ) cells. We evaluated the expression, regulation and signalling of BAFF and APRIL receptors in normal and in CLL cells upon stimulation through CD 40+ IL 4R and BCR . We further analysed the prognostic value of BAFF and APRIL receptors expression in patients with CLL . BCMA expression was significantly higher on CLL cells than on normal B cells. BCR and CD 40+ IL 4R stimulation promoted an increase in TACI and BCMA expression, cell viability and activation in normal B cells. A similar effect was observed in CLL cells after CD 40+ IL 4R but not BCR stimulation. BCMA expression correlated with unmutated IGHV genes, poor‐risk cytogenetics, and short progression‐free survival. These findings further characterize the link between CD 40+ IL 4R regulatory signals, BAFF , APRIL and their receptors and the survival of leukaemic cells and clinical features of CLL .