Polyclonal B-cell proliferation

Benign polyclonal B-cell proliferation (55%) is characterized by a benign proliferation of B lymphocytes, without cytogenetic anomalies or immunoglobulin-gene rearrangement. It is a form of infectious mononucleosis that appears several weeks after an intensification of the immunosuppressive regimen. 

Polyclonal B-cell proliferation with malignant characteristics (30% of lymphomas) has a clinical picture at onset similar to that of benign proliferations. 

Mitogenic effects of endotoxin free substances were screened with the lymphocyte transformation test. In this test the rate of lymphocyte proliferation was quantified by determination of the incorporation of [ H]-thymidine into the DNA of human lymphocytes. Stimulation of lymphocytes was measured with or without coincubation of lectins as mitogens such as concanavalin A (ConA) and phytohemagglutinin (PHA). Saponins such as crude Quillaja saponins, quillayanin, Quil A and gly-cyrrhizic acid (4) have the capacity to induce cell proliferation in lymphocyte cultures at very low concentrations [51]. Induction of B cell proliferation was obtained with crude saponin, T cell proliferation with Quil A, and quillayanin and gly-cyrrhizic acid equally stimulated both T and B lymphocytes. The selective proliferation of subtypes of lymphocytes correlated with restimulation responses by polyclonal mitogens (ConA, PHA), and lipopolysaccharide (LPS). 

The effects of dry stem crude extracts (DSCE) of Tinospora cordifolia and a related plant Tinospora malabarica have been shown to contain polyclonal B cell activators which are assumed to be polysaccharides. The DSCE were prepared by boiling the powdered stems in water followed by treatment with 10% trichloroacetic acid and filtration. The supernatant was further precipitated with acetone, and then fractionated on Sephadex G-200 and Sephacryl S-400 columns. The effects of these fractions were evaluated by culturing lymphocytes in vitro for 48 h in a 5% CO2 environment. Proliferation was estimated by pulsing 2x 10 cells with 1 iCi H-thymidine for 16 h and its incorporation measured by liquid scintillation counting. It was found that DSCE was mitogenic for lymphocytes from lymph node and spleen, while thymocytes, bone marrow cells and peripheral blood cells responded poorly [15]. 

It was demonstrated in the BN rat that mercuric chloride induced a T-dependent polyclonal activation of B cells [181]. Helper/inducer T cells exposed to mercuric chloride either in vivo or in vitro could induce the proliferation of normal autologous T lymphocytes. Normal syngeneic Ia+ cells were necessary for this proliferation [194]. In BN rats lacking T cells, no auto-... 

Filariasis We already discussed about the effects of ES-62 on experimental models of human diseases. The canine filarial nematode Dirofilaria immitis-AtmtA antigen (DiAg) is a purified 15kDa protein able to induce antigen non-specific IgE in rats and mice, as well as polyclonal proliferation of B cells. A timely treatment of NOD mice at 6 weeks of life with DiAg completely prevented the insulin-dependent... 

In assays to assess the immunomodulatory activity of a polysaccharide isolated from white mulberry root bark, the compound was found to enhance proliferation of splenic lymphocytes in a synergistic manner in the presence of mitogens. However, the compound suppressed primary IgM antibody production from B cells, which was activated with lipopolysaccharide, a polyclonal activator, or immunized with a T-cell-dependent antigen, sheep red blood cells (Kim et al. 2000). 

Autoreactive anti-class II T cells have been detected in BN rats injected with HgCl2 or gold salts. In addition, in the latter, T-cell lines have been obtained. We have shown that they are CD4+CD8-, that they proliferate in the presence of syngeneic and not allogeneic APCs, and that their proliferation is completely abolished in the presence of an anti-class II monoclonal antibody. In addition, these cells are able to cooperate in vitro with normal BN B cells to trigger a rise in Ig and IgE production as well as the synthesis of anti-laminin, anti-DNA, and anti-TNP antibodies, which are all markers of the disease (Castedo et al. 1992). These data suggest that these T cells are at play in the B-cell polyclonal activation in vivo. 

Ro41-5253 also counteracted the ability of trans-KA to induce both HL-60 cell differentiation and B-lymphocyte polyclonal activation [77] and to inhibit tumor cell-induced angiogenesis [126], results that confirm the importance of RARa in cell differentiation and proliferation. 

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