title: Regulatory effects of novel neurotrophin-1/b cell-stimulating factor-3 (cardiotrophin-like cytokine) on B cell function.
abstract: We describe regulatory effects that a novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3; also reported as cardiotrophin-like cytokine) has on B cell function. NNT-1/BSF-3 stimulates B cell proliferation and Ig production in vitro. NNT-1/BSF-3-transgenic mice, engineered to express NNT-1/BSF-3 in the liver under control of the apolipoprotein E promoter, show B cell hyperplasia with particular expansion of the mature follicular B cell subset in the spleen and the prominent presence of plasma cells. NNT-1/BSF-3-transgenic mice show high serum levels of IgM, IgE, IgG2b, IgG3, anti-dsDNA Abs, and serum amyloid A. NNT-1/BSF-3-transgenic mice also show non-amyloid mesangial deposits that contain IgM, IgG, and C3 and are characterized by a distinctive ultrastructure similar to that of immunotactoid glomerulopathy. NNT-1/BSF-3-transgenic mice produce high amounts of Ag-specific IgM, IgA, and IgE and low amounts of IgG2a and IgG3. Normal mice treated with NNT-1/BSF-3 also produce high amounts of Ag-specific IgE. NNT-1/BSF-3 regulates immunity by stimulating B cell function and Ab production, with preference for Th2 over Th1 Ig types.
authors.affiliation: Amgen, Inc., Thousand Oaks, CA 91320, USA. gsenaldi@amgen.com
authors.forename: Giorgio
authors.initials: G
authors.lastname: Senaldi
authors.forename: Marina
authors.initials: M
authors.lastname: Stolina
authors.forename: Jane
authors.initials: J
authors.lastname: Guo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Faggioni
authors.forename: Susan
authors.initials: S
authors.lastname: McCabe
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Kaufman
authors.forename: Gwyneth
authors.initials: G
authors.lastname: Van
authors.forename: Weilong
authors.initials: W
authors.lastname: Xu
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Fletcher
authors.forename: Thomas
authors.initials: T
authors.lastname: Boone
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Chang
authors.forename: Ulla
authors.initials: U
authors.lastname: Sarmiento
authors.forename: Russell C
authors.initials: RC
authors.lastname: Cattley
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D005260:Female; D007668:Kidney / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; C121169:cardiotrophin-like cytokine