Impaired IgA class switching in APRIL-deficient mice.
The tumor necrosis factor (TNF) family member APRIL binds to the receptors BCMA on B cells and TACI on B and T cells. To investigate the role of APRIL in immunity, we generated APRIL-deficient mice. APRIL(-/-) mice have normal T and B lymphocyte development, normal T and B cell proliferation in vitro, but increased numbers of CD44(hi)CD62L(lo) CD4(+) effector/memory T cells and increased IgG responses to T-dependent antigens. Serum IgA levels were significantly decreased, and serum IgA antibody responses to mucosal immunization with TD antigens and to type 1 T-independent antigens were impaired in APRIL(-/-) mice. APRIL by itself induced IgA as well as IgG1 isotype switching in CD40-deficient IgM(+)IgD(+) sorted B cells. These results suggest that APRIL down-regulates T cell-dependent antibody responses and promotes IgA class switching.
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Emanuela
E
Castigli
Sumi
S
Scott
Fatma
F
Dedeoglu
Paul
P
Bryce
Haifa
H
Jabara
Atul K
AK
Bhan
Emiko
E
Mizoguchi
Raif S
RS
Geha
D000818:Animals; D000941:Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology / Q000502:physiology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology* / Q000502:physiology; D017578:Immunoglobulin Class Switching / Q000276:immunology* / Q000502:physiology; D008214:Lymphocytes / Q000276:immunology / Q000502:physiology; D008221:Lymphoid Tissue; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
C490341:ANP32B protein, human; D000941:Antigens; D007070:Immunoglobulin A; D009479:Neuropeptides; D009687:Nuclear Proteins