D for the production of allergen-specific IgE in an experimental asthma mouse model (17). The adjuvant effect of iNKT cells on humoral immune responses is antigen-specific. Co-administration with the iNKT cell agonist ligand -galactosylceramide (-GC)5 with immunizing antigen to mice results in enhanced production of antibodies certain for the antigen (180). This support provided by iNKT cells final results inside the induction of long-lived antibody-secreting plasma cells, affinity maturation and also the generation of memory B cells (202). iNKT cells may also provide assist for B cells distinct for lipid-containing antigens internalized by means of the BCR (23, 24). Such B cell aid benefits within the formation of extrafollicular plasmablasts and germinal centres, affinity maturation and robust IgG antibody responses but not long-lived memory cells (25). Although iNKT cells express semi-invariant TCRs, they can be divided into distinct populations according to CD4 and CD8 expression. Humans have varying ratios of CD4+CD8- (CD4+), CD4-CD8– (double-negative or DN)5 and CD4-CD8+- (CD8+) iNKT cells (11, 13, 26). CD4+ iNKT cells release by far the most Th2 cytokines and CD8+ and DN iNKT cells predominantly exhibit Th1 phenotypes and cytotoxic activity (11, 13, 27). To date, two studies (28, 29) have examined the relative contributions of human iNKT cells subsets to BNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript5Abbreviations made use of in this paper: Breg, regulatory B cell; CBA, cytometric bead array; DC, dendritic cell; DN, double adverse CD4-CD8-; FMO, fluorescence minus one particular (flow cytometry control); -GC, -galactosylceramide; iDC, immature dendritic cell; iNKT cells, invariant organic killer T cells; MFI, imply fluorescence intensity; MZB, marginal zone B cells; PPD, purified protein derivative of tuberculin; SEB, Staphylococcal enterotoxin B; TFH cell, follicular helper T cell.Secnidazole J Immunol. Author manuscript; accessible in PMC 2014 October 19.Zeng et al.Pagecell aid and identified that both CD4+ and CD4- iNKT cells similarly induced B cell proliferation, but CD4+ iNKT cells induced greater levels of antibody production.Larotrectinib NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptIn addition to their roles in antibody production, B cells are potent APCs that could prime CD4+ T cells without the participation of DCs or macrophages (30).PMID:24982871 Equivalent to DC, B cells can produce each Th1- and Th2-type cytokines and may be polarized towards one or the other subset subsequent to interaction with CD4+ Th1 or Th2 cells (31). The exceptional skills of iNKT cells to selectively secrete Th1, Th2, Th17 or regulatory T cell cytokines (103) and to induce DC maturation (7, 8, 32) led us to hypothesise that iNKT cells may possibly exert stimulatory and/or regulatory manage more than antigen presentation and T cell activation by B cells. Right here we’ve examined the outcomes of culturing human peripheral B cells with expanded autologous iNKT cells or sorted CD4+, CD8+ and DN iNKT cell subsets in vitro, inside the absence or presence of -GC. We show that the iNKT cell subsets differentially induce phenotypic differentiation, antibody secretion and T cell stimulation by B cells. We also show that CD4+ iNKT cells promote the improvement of cells with phenotypes of regulatory B (Breg)5 cells as well as the production of IL-10 by some B cells. Therefore, CD4+, CD8+ and DN iNKT cells can differentially market T cell or antibody responses by means of their interactions with B cells. This observation has implications for.
