Impaired IgA class switching in APRIL-deficient mice

Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3903-8. doi: 10.1073/pnas.0307348101. Epub 2004 Feb 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / immunology
  • Cell Division / immunology
  • Cell Division / physiology
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology*
  • Immunoglobulin A / physiology
  • Immunoglobulin Class Switching / immunology*
  • Immunoglobulin Class Switching / physiology
  • Lymphocytes / immunology
  • Lymphocytes / physiology
  • Lymphoid Tissue
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neuropeptides / deficiency*
  • Neuropeptides / genetics
  • Neuropeptides / physiology
  • Nuclear Proteins / deficiency*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Reverse Transcriptase Polymerase Chain Reaction


  • ANP32B protein, human
  • Antigens
  • Immunoglobulin A
  • Neuropeptides
  • Nuclear Proteins