Abstract
Studies in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), have shown that regulatory B cells modulate the course of the disease via the production of suppressive cytokines. While data indicate a role for transforming growth factor (TGF)-β1 expression in regulatory B cell functions, this mechanism has not yet been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B–TGF-β1−/−) were tested in EAE induced by recombinant mouse myelin oligodendrocyte glycoprotein (rmMOG). In this model, B–TGF-β1−/− mice showed an earlier onset of neurologic impairment compared to their littermate controls. Exacerbated EAE susceptibility in B–TGF-β1−/− mice was associated with augmented CNS T helper (Th)1/17 responses. Moreover, selective B cell TGF-β1–deficiency increased the frequencies and activation of myeloid dendritic cells, potent professional antigen-presenting cells (APCs), suggesting that B cell-derived TGF-β1 can constrain Th1/17 responses through inhibition of APC activity. Collectively our data suggest that B cells can down-regulate the function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1, findings that may be relevant to B cell-targeted therapies.
Highlights
B cell-derived plasma cells did not express IL-35 were shown to lose their ability to recover from EAE22
The role of transforming growth factor (TGF)-β1 production by B cells was investigated in EAE induced by recombinant mouse MOG (rmMOG) protein, a protocol that activates the cellular component of B cell immunity[14]
There was a significant difference between B–TGF-β1+/+ and B–TGF-β1−/− mice, as shown by the comparison of the mean EAE scores monitored over a period of 25 days (Fig. 1a)
Summary
B cell-derived plasma cells did not express IL-35 were shown to lose their ability to recover from EAE22. B–TGF-β1−/− mice expressed a higher frequency of CD11c+CD11b+ conventional myeloid splenic dendritic cells (DCs), as well as increased surface expression levels of MHC class II and CD86 molecules by those cells This suggests that TGF-β1 –producing B cells restrained disease progression, at least partly, by affecting the immunogenic functions of myeloid DCs. This suggests that TGF-β1 –producing B cells restrained disease progression, at least partly, by affecting the immunogenic functions of myeloid DCs These data show that TGF-β1 production by B cells is an important regulatory mechanism in T cell-mediated autoimmune diseases such as EAE and MS
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