Polyclonal activation

Substances that cause cells, particularly lymphocytes, to undergo cell division. Mitogens are also referred to as polyclonal activators, since they stimulate proliferation of lymphocytes irrespective of their clonal origin. The best known mitogens are phytohemagglutinines isolated from certain plants. 

Compared to people in a noncontaminated area, plasma IgG levels were also significantly decreased in proportion to increasing plasma levels of TCDD in a cohort exposed in an industrial accident in Seveso, Italy.118 There was no effect on IgM or IgA levels, or on complement levels IgE was not measured. In separate studies, in vitro exposure to TCDD enhanced the spontaneous production of IgE by B cells isolated from atopic but not non-atopic individuals, but did not affect the levels of other isotypes.119 Other recent studies have reported small changes in immune cells from individuals exposed occupationally to PHAH.120121 For example, compared to unexposed controls, a cohort of men exposed occupationally to TCDD had diminished IFNy production in a recall response to tetanus toxin, while IFNy production following polyclonal activation was unaffected.120 This observation is consistent with mouse studies, in which antigen-specific responses are highly suppressed by TCDD, but mitogen-driven T cell responses are less susceptible to impairment.83 88122123... 

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-... 

These and the following examples show the strongest catalytic effects for ester hydrolysis obtained so far by the imprinting method. Compared to antibodies, such imprinted polymers are less efficient by just one order of magnitude (see later results). This is especially remarkable since we used polyclonal active sites and rigid, insoluble polymers. It should also be mentioned that these hydrolyses occur with non-activated phenol esters and not, as in nearly all other reported cases, with activated 4-nitrophenyl esters. 

Chemicals may also cause an autoimmune kidney disease in the context of polyclonal B- and/or T-ceU activation. This will lead to B-ceU polyclonal activation with production of auto-antibodies since, normally... 

Savignac M, Badou A, DelmasC, Subra JF, De Cramer S, Paulet P, Cassar G, Druet P, Saoudi A, Pelletier L Gold is aTcell polyclonal activator in BN and LEW rats but favors IL-4 expression only in autoimmune prone BN rats. Eur. J. Immunol. 2001 31 2266-2276. 

T-independent immunogens (reviewed by Feldmann, 1974) usually have multiple copies of the same determinant and are, therefore, capable to react with several receptors on the same B cell ( capping ), which activates the cell. At high concentrations, T-independent immunogens may become polyclonal activators of B cells and act as mitogens of B cells. T-dependency may vary with the host haptenated polyacrylamide beads are T-independent in the mouse (Feldmann et al., 1974) and T-dependent in man (Galanaud, 1979). 

Bernasconi NL, Traggiai E, Lanzavecchia A Maintenance of serological memory by polyclonal activation of human memory B cells. Science 2002 298 2199-2202. 

Switching to classes other than IgD is most obvious in activated B cells. Extensive studies have been performed on mouse B cells that have been polyclonally activated by bacterial lipopolysaccharide (LPS) [2,16-18] or by both LPS and switch factors , i.e. certain lymphokines produced by T lymphocytes [6-9]. Antigen stimulation in vitro (e.g. [19]) and mitogenic stimulation of human B cells (e.g. [20])... 

In addition, the fact that several rounds of proliferation are required for the switching of polyclonally activated and immunoglobulin secreting plasmablasts [21-23] suggests that DNA rearrangement precedes the phenotypic switch. 

Fig. 1. Quantitative restriction analysis for the evaluation of class switch recombination in polyclonally activated B cells. The rearrangement of the Syl region is reflected by the disappearance of the S7l germline restriction fragment (). This is measured by determination of the ratio of hybridisation intensities of Sr, and a reference probe. The loss of Sy, is calculated from the comparison of intensity ratios in lane A (liver DNA) and B (activated B cells). Further details are given in Section 4.3.1. of this chapter.

Class-switch rearrangement of the IgH loci of polyclonally activated B cells... 

In polyclonally activated B cells class switch recombination precedes or rapidly follows the switch in CH-gene expression. Switching by a differential RNA splicing mechanism would apply for a very short period, if at all. The frequency of cells expressing surface IgG3 begins to increase after day 3 of LPS stimulation and already by day 6 about half of the IgH loci of these cells have performed switch recombination. 

Saoudi A, Castedo M, Nochy D., Mandet C, Pasquier R, Druet P, Pelletier L. Self reactive anti-class II Th2 cell lines derived from gold salt-injected rats trigger B cell polyclonal activation and transfer autoimmunity in CD8-depleted normal syngeneic recipients. Eur J Immunol 1995 25 1972-1979. 

Mahon, A.C., Gebre, N., and Nurlign, A. 1990, The response of human B cells to Mycobacterium leprae. Identification of target antigens following polyclonal activation in vitro. International Immunology 2 803-812. 

Izui, S., McConahey, P.J. and Dixon, F.J. (1978). Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J. Immunol, 121, 2213-2219... 

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