Impaired IgA class switching inn APRIL-deficient mice

Emanuela Castigli, Sumi Scott, Fatma Dedeoglu, Paul Bryce, Haifa Jabara, Atul K. Bhan, Emiko Mizoguchi, Raif S. Geha*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

325 Scopus citations

Abstract

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 CD44hiCD62Llo 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.

Original languageEnglish (US)
Pages (from-to)3903-3908
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number11
DOIs
StatePublished - Mar 16 2004

ASJC Scopus subject areas

  • General

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