5A and B). Similarly, when BAFF activity was prevented by the addition of a specific BAFF neutralizing Ab to PBMC cultures, a reduction in the TLR7-stimulated IgM and IgG production was obtained (Supporting Information Fig. 3). A different picture was found when Ig release was measured upon TLR9 triggering in either monocyte-depleted PBMCs or whole PBMCs treated with anti-BAFF Ab. Indeed, an enhanced release

of both IgM and IgG was observed in response to TLR9 stimulation in the absence of monocytes while the neutralization of BAFF poorly affected Ig Cytoskeletal Signaling inhibitor production (Fig. 5A and B and Supporting Information Fig. 3, respectively). This result was not obvious and, at this stage, it is difficult to explain but it suggests that monocytes could be associated to a negative feedback loop on TLR9-driven B-cell differentiation while they positively act on the TLR7 responsiveness of Ig-producing Selleckchem Napabucasin B cells. Thus, we can envisage that changes in the basal and/or TLR-induced cytokine milieu of in vivo IFN-β-conditioned PBMCs could profoundly impact on Ig production from B cells in response to TLR7 or TLR9 stimulation. Collectively, these findings demonstrate that the cross-talk between monocytes and B cells is essential for the release of an effective humoral immune response in the context of

TLR7 stimulation affecting the maturation and differentiation status of B lymphocytes into Ig-secreting cells. Over the past decade, there has been growing understanding and acceptance of the pathological involvement

of B cells and humoral response in MS [1, 2]. The demonstration that peripheral B-cell depletion leads to a rapid decline in disease activity in MS is the strongest evidence of the central role of these cells in MS autoimmunity [9, 11]. However, the key question that still remains unsolved is when and how in the Ribonucleotide reductase life of an individual B cell does provide immunopathogenic support or arise as a disease-relevant cell type in MS. In this study, we investigated whether IFN-β targets B lymphocytes and modulates their functions contributing to the protective effects of this treatment. Only a few studies have thus far addressed this point and most have investigated the ability of highly purified B cells from MS patients to present antigens and subsequently regulate T-cell responses [28, 29]. In contrast, we studied whether IFN-β therapy would regulate the maturation and differentiation of B cells into Ig-secreting cells in response to TLR7 or TLR9 stimulation. Indeed, it has been shown that TLR triggering is necessary for extensive human naïve B-cell proliferation, isotypic switching, and production of Abs providing the third signal upon BCR cross-linking by antigen and interaction with T helper cells [30].