B-lymphocyte stimulator

The effects of different OTC in human immune tissue were studied in isolated tonsil B cells. Non-stimulated B cells were killed by 100 nM concentration of all tested OTC after 8 h in vitro culture. Organotin derivatives also decreased the proliferation of tonsillar B lymphocytes stimulated with Staphylococcus aureus Cowan 1 and IL-2, when present at 100 nM and higher concentrations. Increased phosphatidylserine exposure demonstrated that 100 nM concentration of triphenyltin chloride and dibutyltin dichloride induced B cells to die by apoptosis38. 

Schaniel, C., Sallusto, F., Ruedl, C., Sideras, P., Melchers, F., and Rolink, A. G. (1999). Three chemokines with potential functions in T lymphocyte-independent and -dependent B lymphocyte stimulation. Eur. J. Immunol. 29, 2934-2947. 

The cytokines IL-2, IL-5 and IL-6 enhance IL-4-induced secretion of IgE by human B lymphocytes (Vercelli etal., 1989 Jabuia et al., 1990), and probably act as permissive stimuli through their non-specific activation of B cells, since there is no evidence that they can induce IgE switching. Several cytokines also inhibit IgE synthesis by human B lymphocytes in vitro. Both IFN7 and IFNa specifically inhibit IgE secretion by B lymphocytes cultured with Epstein-Barr virus (Thyphronitis et al., 1989), although neither of these cytokines inhibits IL-4-dependent induction of increased steady-state concentrations of germline e-chain RNA in B lymphocytes (Gauchat etal., 1990). IL-12 has been reported to reduce IgE synthesis by B lymphocytes stimulated with IL-4 and cortisol (Kiniwa etal., 1992). 

Fabris M, Quartuccio L, Vital E, Pontarini E, Salvin S, Fabro C et al (2013) The TTTT B lymphocyte stimulator promoter haplotype is associated with good response to rituximab therapy in seropositive rheumatoid arthritis resistant to tumor necrosis factor blockers. Arthritis Rheum 65 88-97... 

B lymphocyte stimulator (BLyS) [10], a novel member of the TNF ligand superfamily that is fundamental for B cell maturation and survival. The possible implications of all these observations need to be explored by in vivo studies, but it is clear that they might have an important biological significance in health and disease. 

BLys B lymphocyte stimulator B-cell activating factor, BAFF... 

Observational studies An evaluation of the safety profile of long-term belimumab (target BLys, B-lymphocyte stimulator) therapy in patients with active lupus erythematosus showed that through 4 years, or 1165 cumulative patient-years, of belimumab administration the most common adverse events included arthralgia, upper respiratory... 

A B lymphocyte is a specific type of white blood cell (leucocyte) derived from bone marrow stem cells. Each B lymphocyte expresses an immunoglobulin (antibody) specific for a particular antigen. Following antigenic stimulation, a B lymphocyte may differentiate and multiply into plasma cells that secrete large quantities of monoclonal antibody. 

A cytokine, secreted by TH2-cells, stimulates B-cells in different stages of their development. It may act as a growth factor or as a differentiation factor, causing B-lymphocytes to switch antibody to IgE. In T-cells it causes differentiation into TH2-cells. 

A lipopolysaccharide (LPS) is any compound consisting of covalently linked lipids and polysaccharides. The term is used more frequently to denote a cell wall component from Gram-negative bacteria. LPS has endotoxin activities and is a polyclonal stimulator of B-lymphocytes. 

NF-xB, originally defined as the enhancer of kappa light-chain expression in B lymphocytes, is a hcterodimeric protein that can rapidly activate several genes associated with the inflammatory process (reviewed by Schreck et al., 1992). The DNA binding, nuclear form, of NF-xB is a heterodimer composed of one Rel-A (65 kD) and one p50 (50 kD) subunit. However, both subunits can form homodimers that also have DNA-binding activity. The inactive form of NF-xB in non-stimulated cells is localized to the cytoplasm of resting cells, and is bound to its inhibitor IxB. 

Proinflammatory TNF-a Macrophages, monocytes, B lymphocytes, T lymphocytes, fibroblasts Induces IL-1, IL-6, IL-8, GM-CSF stimulates fibroblasts to release adhesion molecules... 

IL-1 Macrophages, monocytes, endothelial cells, B lymphocytes, activated T lymphocytes Stimulates fibroblasts and chondrocytes to release matrix metalloproteinases... 

Inhibition and stimulation of LOX activity occurs as a rule by a free radical mechanism. Riendeau et al. [8] showed that hydroperoxide activation of 5-LOX is product-specific and can be stimulated by 5-HPETE and hydrogen peroxide. NADPH, FAD, Fe2+ ions, and Fe3+(EDTA) complex markedly increased the formation of oxidized products while NADH and 5-HETE were inhibitory. Jones et al. [9] also demonstrated that another hydroperoxide 13(5)-hydroperoxy-9,ll( , Z)-octadecadienoic acid (13-HPOD) (formed by the oxidation of linoleic acid by soybean LOX) activated the inactive ferrous form of the enzyme. These authors suggested that 13-HPOD attached to LOX and affected its activation through the formation of a protein radical. Werz et al. [10] showed that reactive oxygen species produced by xanthine oxidase, granulocytes, or mitochondria activated 5-LOX in the Epstein Barr virus-transformed B-lymphocytes. 

Most cytokines are pleiotropic, i.e. can affect a variety of cell types. Moreover, the effect that a cytokine has on one cell type may be the same or different to its effect on a different cell type. IL-1, for example, can induce fever, hypotension and an acute phase response. G-CSF is a growth factor for neutrophils, but it is also involved in stimulating migration of endothelial cells and growth of haematopoietic cells. IFN-y stimulates activation and growth of T- and B-lymphocytes, macrophages, NK cells, fibroblasts and endothelial cells. It also displays weak anti-proliferative activity with some cell types. 

Additional molecular mechanisms must also mediate IFN-y effects, as it promotes a marked clinical improvement in some CGD patients without enhancing phagocyte activity. IFN-y s demonstrated ability to stimulate aspects of cellular and humoral immunity (e.g. via T- and B-lymphocytes), as well as NK cell activity, is most likely responsible for these observed improvements. 

IL-2 acts as a critical autocrine growth factor for T-cells, and the magnitude of the T-cell response is largely dependent upon the level of IL-2 produced. IL-2 also serves as a growth factor for activated B-lymphocytes. In addition to promoting proliferation of these cells, IL-2 (as well as some other interleukins) stimulates enhanced antibody production and secretion. In this way, it effectively potentates the humoral immune response. 

Initial stages in the production of murine monoclonals entail administration of the antigen of interest to a mouse. This is followed by sacrifice and recovery of activated B-lymphocytes from the spleen. A similar approach to the production of human monoclonals would be unethical. Administration of some antigens to humans could endanger their health. Although B-lymphocytes could be obtained from the peripheral circulation, the majority of these are unstimulated, and recovery of (stimulated) B-lymphocytes from the spleen is impractical. 

Acid acetone extracts of human and rodent leukocytes (RBL-cells) have been found to contain immunoreactive SOM (iSOM) and immunoreactive SP (iSP) as determined by radioimmunoassay [144], Quantities of the peptides varied from 325 pg iSOM/107 cells for human monocytes and 272 pg iSOM/107 cells for RBL-cells to 4.4 pg iSOM/107 cells for human T cells. iSP was highest in murine bone marrow-derived mast cells (64 pg iSP/107 cells) and RBL-cells (23 pg iSP/107 cells) and lowest in human T and B lymphocytes (2.5 and 1.2 pg iSP/107 cells, respectively). Interestingly, the murine bone marrow-derived mast cells had the highest ratio of iSP to iSOM. Preliminary chromatographic results show a large and a small SOM (SOM-28 and SOM-14, respectively). SOM-14 (3 x 10 9 M) has been shown to inhibit histamine release and LTC4 generation from murine bone marrow-derived mast cells stimulated by anti-IgE serum [144]. 

Klaus, G.G.B. and Hawrylowicz, C.M. (1984). Cell-cycle control in lymphocyte stimulation. Immunol. Today 5 15-19. 

When B lymphocytes are stimulated by antigen they develop into plasma cells. The receptor of plasma cells can be secreted from the cell because some of these molecules lack the hydrophobic domain that normally anchors the receptor to the plasma membrane. These secreted molecules are immunoglobulins or antibodies and have a common structure (Fig. 1.8). They are found in a variety of bodily fluids and in many tissues. 

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