title: Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL.
abstract: Hodgkin lymphoma (HL) originates from the clonal expansion of malignant Hodgkin and Reed-Sternberg (HRS) cells. These B-cell-derived elements constitute less than 10% of the tumoral mass. The remaining tissue is comprised of an inflammatory infiltrate that includes myeloid cells. Myeloid cells activate B cells by producing BAFF and APRIL, which engage TACI, BCMA, and BAFF-R receptors on the B cells. Here, we studied the role of BAFF and APRIL in HL. Inflammatory and HRS cells from HL tumors expressed BAFF and APRIL. Unlike their putative germinal center B-cell precursors, HRS cells lacked BAFF-R, but expressed TACI and BCMA, a phenotype similar to that of plasmacytoid B cells. BAFF and APRIL enhanced HRS cell survival and proliferation by delivering nonredundant signals via TACI and BCMA receptors through both autocrine and paracrine pathways. These signals caused NF-kappaB activation; Bcl-2, Bcl-xL, and c-Myc up-regulation; and Bax down-regulation, and were amplified by APRIL-binding proteoglycans on HRS cells. Interruption of BAFF and APRIL signaling by TACI-Ig decoy receptor, which binds to and neutralizes BAFF and APRIL, or by small-interfering RNAs targeting BAFF, APRIL, TACI, and BCMA inhibited HRS cell accumulation in vitro and might attenuate HL expansion in vivo.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College, Cornell University, 1300 York Ave, Rm C-410, New York, NY 10021, USA.
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.forename: Weifeng
authors.initials: W
authors.lastname: Xu
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Stacey R
authors.initials: SR
authors.lastname: Dillon
authors.forename: Jane A
authors.initials: JA
authors.lastname: Gross
authors.forename: Eric
authors.initials: E
authors.lastname: Sievers
authors.forename: Xugang
authors.initials: X
authors.lastname: Qiao
authors.forename: Paul
authors.initials: P
authors.lastname: Santini
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hyjek
authors.forename: Joong-won
authors.initials: JW
authors.lastname: Lee
authors.forename: Ethel
authors.initials: E
authors.lastname: Cesarman
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Knowles
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
mesh_terms: D053264:B-Cell Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D053301:B-Cell Maturation Antigen / Q000096:biosynthesis* / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020869:Gene Expression Profiling; D006689:Hodgkin Disease / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction; D053303:Transmembrane Activator and CAML Interactor Protein / Q000096:biosynthesis* / Q000235:genetics; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13