title: B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenstrom macroglobulinemia.
abstract: Waldenström macroglobulinemia (WM) is a serious and frequently fatal B-cell malignancy associated with an elevated monoclonal IgM protein in the serum. Many of the mechanisms leading to this disease are not yet known. B-lymphocyte stimulator (BLyS) is a TNF family member that is critical for maintenance of normal B-cell development and homeostasis. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B cells. It also regulates immunoglobulin secretion by normal B cells. To determine the relevance of BLyS in WM, we examined the role of BLyS in WM patient samples. Malignant B cells were found to bind soluble BLyS and variably express the receptors BAFF-R, TACI, and BCMA. We also found expression of BLyS in bone marrow specimens by immunohistochemistry and elevated serum BLyS levels in patients with WM. BLyS, alone or in combination with cytokines that induce immunoglobulin production, was found to increase IgM secretion by malignant B cells. Furthermore, BLyS was found to increase the viability and proliferation of malignant B cells from WM patients. Due to the role of BLyS in WM, strategies to inhibit BLyS may potentially have therapeutic efficacy in these patients.
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. ansell.stephen@mayo.edu.
authors.forename: Sherine F
authors.initials: SF
authors.lastname: Elsawa
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Grote
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ziesmer
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Stacey R
authors.initials: SR
authors.lastname: Dillon
authors.forename: Brandon
authors.initials: B
authors.lastname: Harder
authors.forename: Jane A
authors.initials: JA
authors.lastname: Gross
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
mesh_terms: D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology* / Q000473:pathology
chemical_list: D053264:B-Cell Activating Factor; D007136:Immunoglobulins; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha