In vitro and in vivo activation induces BAFF and APRIL expression in B cells

VT Chu, P Enghard, G Riemekasten… - The Journal of …, 2007 - journals.aai.org
VT Chu, P Enghard, G Riemekasten, C Berek
The Journal of Immunology, 2007journals.aai.org
B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) play key roles in
peripheral B cell survival, maturation, and differentiation. BAFF and APRIL are produced by
a variety of cell types such as macrophages/monocytes and dendritic cells. Our analysis
shows that BAFF mRNA is also expressed in all B cell subsets isolated from bone marrow,
spleen, and peritoneal cavity of BALB/c mice. APRIL expression is restricted to early stages
of B cell development in the bone marrow and the peritoneal B1 subset. Stimulation of B2 …
Abstract
B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) play key roles in peripheral B cell survival, maturation, and differentiation. BAFF and APRIL are produced by a variety of cell types such as macrophages/monocytes and dendritic cells. Our analysis shows that BAFF mRNA is also expressed in all B cell subsets isolated from bone marrow, spleen, and peritoneal cavity of BALB/c mice. APRIL expression is restricted to early stages of B cell development in the bone marrow and the peritoneal B1 subset. Stimulation of B2 and B1 cells with LPS or CpG-oligodeoxynucleotides induced MyD88-dependent plasma cell differentiation and intracellular expression of BAFF and APRIL. Furthermore, activation of B cells up-regulated membrane expression of BAFF. The finding that in vitro activation of B cells is inhibited by the antagonist transmembrane activator and calcium modulator ligand interactor Ig, indicates that BAFF and/or APRIL are released into the culture supernatants. It shows that B cell survival, proliferation, and differentiation are supported by an autocrine pathway. In vivo activation of B cells with a T-dependent Ag-induced BAFF expression in germinal center B cells. In (NZB× NZW) F 1 mice with established autoimmune disease, marginal zone, germinal center B cells, as well as splenic plasma cells expressed high levels of BAFF. In (NZB× NZW) F 1 mice, the continuous activation of B cells and thus overexpression of BAFF and APRIL may contribute to the development of autoimmune disease.
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