Activation of marginal zone B cells from lupus mice with type A (D) CpG-oligodeoxynucleotides

R Brummel, P Lenert - The Journal of Immunology, 2005 - journals.aai.org
R Brummel, P Lenert
The Journal of Immunology, 2005journals.aai.org
Several types of CpG-oligodeoxynucleotides (ODN) have been recently characterized. In
mice, type A (D) CpG-ODNs primarily stimulate macrophages and dendritic cells, but fail to
stimulate B cells. On the contrary, type B (K) CpG-ODNs are excellent B cell activators. Type
C CpG-ODNs combine features of both types A (D) and B (K) CpG-ODNs. Despite cell type
preferences, all CpG-ODNs require the presence of TLR9 for activation. In this study, we
show that a subset of B cells from lupus mice responds to type A (D) CpG-ODN stimulation …
Abstract
Several types of CpG-oligodeoxynucleotides (ODN) have been recently characterized. In mice, type A (D) CpG-ODNs primarily stimulate macrophages and dendritic cells, but fail to stimulate B cells. On the contrary, type B (K) CpG-ODNs are excellent B cell activators. Type C CpG-ODNs combine features of both types A (D) and B (K) CpG-ODNs. Despite cell type preferences, all CpG-ODNs require the presence of TLR9 for activation. In this study, we show that a subset of B cells from lupus mice responds to type A (D) CpG-ODN stimulation vigorously and directly with increased CD25 and CD86 expression and IL-10 secretion. Furthermore, these CpG-ODNs induce high surface IgM expression and promote 50-to 100-fold higher IgM and IgG3 secretion in lupus B cells than in controls. This response is similar to that seen with bacterial DNA stimulation of B cells. Type A (D)-responsive cells are enriched within lupus B cells with the marginal zone (MZ) phenotype. These cells are at least twice more numerous in lupus mice than in controls. The ability of lupus B cells to respond to type A (D) CpG-ODN stimulation is not due to differential TLR9 expression. Therefore, type A (D) CpG-ODNs may contribute to the lupus pathogenesis by inducing MZ-B cell activation, costimulatory molecule expression, and polyclonal Ig secretion. Through increased IL-10 secretion, MZ-B cells may also modify the activity of other cell types, particularly dendritic cells and macrophages.
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