title: APRIL-deficient mice have normal immune system development.
abstract: APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor (TNF) superfamily. APRIL mRNA shows high levels of expression in tumors of different origin and a low level of expression in normal cells. APRIL shares two TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF. BLyS is involved in regulation of B-cell activation and survival and also binds to a third receptor, BR3/BAFF-R, which is not shared with APRIL. Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction. To investigate the physiological role of APRIL, we generated mice that are deficient in its encoding gene. APRIL(-/-) mice were viable and fertile and lacked any gross abnormality. Detailed histological analysis did not reveal any defects in major tissues and organs, including the primary and secondary immune organs. T- and B-cell development and in vitro function were normal as well, as were T-cell-dependent and -independent in vivo humoral responses to antigenic challenge. These data indicate that APRIL is dispensable in the mouse for proper development. Thus, BLyS may be capable of fulfilling APRIL's main functions.
authors.affiliation: Department of Molecular Oncology, Genentech Inc., South San Francisco, California 94080, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Varfolomeev
authors.forename: Frank
authors.initials: F
authors.lastname: Kischkel
authors.forename: Flavius
authors.initials: F
authors.lastname: Martin
authors.forename: Dhaya
authors.initials: D
authors.lastname: Seshasayee
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Lawrence
authors.forename: Christine
authors.initials: C
authors.lastname: Olsson
authors.forename: Lucrece
authors.initials: L
authors.lastname: Tom
authors.forename: Sharon
authors.initials: S
authors.lastname: Erickson
authors.forename: Dorothy
authors.initials: D
authors.lastname: French
authors.forename: Peter
authors.initials: P
authors.lastname: Schow
authors.forename: Iqbal S
authors.initials: IS
authors.lastname: Grewal
authors.forename: Avi
authors.initials: A
authors.lastname: Ashkenazi
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D007107:Immune System / Q000502:physiology*; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000502:physiology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D008565:Membrane Proteins; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha