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J Clin Invest 2002 Jun 15;109(12):1587-1598
Stein JV, Lopez-Fraga M, Elustondo FA, Carvalho-Pinto CE, Rodriguez D, Gomez-Caro R, De Jong J, Martinez-A C, Medema JP, Hahne M.
Department of Immunology and Oncology, Centro Nacional de Biotecnologia, Madrid, Spain. Departamento de Biologia Celular y Molecular, Centro Nacional de Biotecnologia, Madrid, Spain. Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
The TNF-like ligands APRIL and BLyS are close relatives and share the capacity to bind the receptors TACI and BCMA.
BLyS has been shown to play an important role in B cell homeostasis and autoimmunity, but the biological role of APRIL remains less well defined.
Analysis of T cells revealed an activation-dependent increase in APRIL mRNA expression.
We therefore generated mice expressing APRIL as a transgene in T cells.
These mice appeared normal and showed no signs of B cell hyperplasia.
Transgenic T cells revealed a greatly enhanced survival in vitro as well as enhanced survival of staphylococcal enterotoxin B-reactive CD4(+) T cells in vivo, which both directly correlate with elevated Bcl-2 levels.
Analysis of humoral responses to T cell-dependent antigens in the transgenic mice indicated that APRIL affects only IgM but not IgG responses.
In contrast, T cell-independent type 2 (TI-2) humoral response was enhanced in APRIL transgenic mice.
As TACI was previously reported to be indispensable for TI-2 antibody formation, these results suggest a role for APRIL/TACI interactions in the generation of this response.
Taken together, our data indicate that APRIL is involved in the induction and/or maintenance of T and B cell responses.