The crosstalk between the innate and adaptive

immune systems is exemplified by responses involving marginal zone (MZ) B cells or invariant NKT (iNKT) cells. Indeed, these lymphocyte subsets mount very early, innate-like adaptive responses after recognizing microbial carbohydrate and glycolipid antigens via both germline-encoded and somatically recombined receptors [[3-5]]. B cells confer immune protection by producing antibody molecules, also known as immunoglobulins (Igs), which can recognize antigen through either low- or high-affinity binding modes. Bone marrow B-cell selleck chemicals precursors generate Ig recognition diversity by undergoing V(D)J gene recombination, an antigen-independent process that utilizes recombination activating gene (RAG) endonucleases to juxtapose noncontiguous variable (V), diversity (D) and joining (J) gene fragments into functional V(D)J genes encoding the antigen-binding V region of Ig molecules (reviewed in [[6]]). After further maturation events, multiple subsets of mature B cells co-expressing IgM and IgD emerge from GSI-IX research buy the

bone marrow and colonize different compartments of secondary lymphoid organs to initiate the antigen-dependent phase of B-cell development. In general, conventional follicular B cells, which are also called B-2 cells, predominantly participate in T-cell-dependent (TD) antibody responses to highly specific determinants usually associated with microbial proteins (reviewed in [[7]]). TD responses unfold in the germinal center of lymphoid follicles and generate high-affinity antibodies through a TD pathway that involves activation of B cells by follicular helper T (TFH) cells. This germinal center-associated

T-cell subset expresses the inducible T-cell costimulator (ICOS) receptor, the chemokine receptor CXCR5, the programmed cell death-1 (PD-1) inhibitory receptor and the transcription factor Bcl6 [[8-15]]. TFH cells provide help to B cells via CD40 ligand (CD40L) and cytokines such as IL-21, IL-4, and IL-10 [[16-19]]. However, recent findings indicate that follicular antibody responses further involve additional T-cell subsets, Mannose-binding protein-associated serine protease including follicular regulatory T (TFR) cells and iNKT cells [[4, 5, 20-22]]. Unlike follicular B cells, certain subsets of extrafollicular B cells such as B-1 cells, splenic MZ B cells (also referred to as IgM memory B cells in humans) and bone marrow perisinusoidal B cells predominantly give rise to rapid T-cell-independent (TI) antibody responses to highly conserved carbohydrate and glycolipid determinants associated with microbes [[3, 23-30]]. TI antibody responses usually unfold at the mucosal interface or in the splenic MZ and generate polyspecific and low-affinity antibodies through a TI pathway involving the interaction of B cells with DCs, macrophages, and granulocytes [[3, 30-34]].