They also revealed that these elevated B cells in SAMP1/Yit mice exhibited pathogenic phenomena rather than a regulatory role

by abrogating regulatory T-cell functions. Therefore, they speculate that the B cells may be the primary check details cell population responsible for over-riding anti-inflammatory or regulatory signals in vivo and promoting the development of SAMP1/Yit ileitis. With the essence of their speculation of impeding the regulatory signals, here we proceeded to focus on IL-10 production by B cells from SAMP1/Yit and compared it with that of control AKR/J mice and added a maiden finding of decreased production of IL-10 in TLR-activated intestinal B cells of SAMP1/Yit mice, which may alter the immune regulatory phenotypes leading to intestinal inflammation. Apart from this, other studies have found that FK506 ic50 a regulatory subset of MLN B cells is involved in intestinal immune regulation by

recruiting regulatory T cells,56 so disorders of such functions of MLN B cells may also be associated with the pathogenesis of ileitis in SAMP1/Yit mice. The notion of specific cell surface markers that characterize regulatory B cells is controversial. Potential cell surface markers, such as CD5+ (B-1a), CD11blow CD5− IgD+, CD1bhigh CD21high (marginal zone B cells), and CD21high CD23high (T2-marginal zone precursor B cells), have been reported to specifically identify the phenotype of IL-10-producing regulatory B cells.21,32,33 Recently, Tedder and colleagues evaluated spleen B cells and found a rare CD1dhigh CD5+ B subset (1–2% of spleen B cells) with IL-10-producing

ability.33,42 Furthermore, that study also revealed that CD19-mediated signalling is required for the production of IL-10 by CD1dhigh CD5+ B cells in the Aurora Kinase spleen. In the present study, we observed that MLN B cells producing IL-10 and TGF-β were mainly located in a population characterized by the cell surface markers CD1d+ in both SAMP1/Yit and AKR/J mice. However, we could not specifically identify the regulatory subset of MLN B cells by evaluating cell surface expression of CD5. More recently, Yanaba et al.57 demonstrated that spleen B cells expressing IL-10 were also found in a CD1dhigh CD5− CD19+ subset, though the number of those cells was relatively low. Organ specificity, signalling pathways via CD19, CD40 and TLRs, and other unknown factors may influence the characterization of regulatory B cells producing IL-10. Additional investigations are necessary to clearly understand these issues. In summary, we investigated the presence of a subset of regulatory B cells expressing IL-10 and TGF-β1 in mouse intestines, as well as its role in the pathogenesis of ileitis in SAMP1/Yit mice. A decreased level of production of IL-10 and TGF-β1 by TLR-activated intestinal B cells was observed in SAMP1/Yit mice, which failed to inhibit IL-1β production by macrophages.