APRIL-deficient mice have normal immune system development.
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.
Varfolomeev
Eugene
E
Department of Molecular Oncology, Genentech Inc., South San Francisco, California 94080, USA.
Kischkel
Frank
F
Martin
Flavius
F
Seshasayee
Dhaya
D
Wang
Hua
H
Lawrence
David
D
Olsson
Christine
C
Tom
Lucrece
L
Erickson
Sharon
S
French
Dorothy
D
Schow
Peter
P
Grewal
Iqbal S
IS
Ashkenazi
Avi
A
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
D008565:Membrane Proteins; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha