B-cells polyclonal activation

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. 

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. 

Mercury or gold triggers anti-mercury and anti-gold T cells, respectively. As described in the hypersensitivity reactions, these cells could recognize either class II modified by mercury or gold or a self-peptide presented by a given MHC class II molecule. At variance with what is found in DTH reactions, in the presence of IL-4, these cells would differentiate into TH2 cells specialized in B-cell help. Autoreactive anti-class II T cells able to interact with native class II molecules expressed by normal B cells would be induced in turn as has been described in other situations (Lin et al. 1991). These latter cells would be responsible for the B-cell polyclonal activation induced by the transfer of T cells from diseased rats into normal BN recipients. 

Castedo M, Pelletier L, Druet P (1992) A role for autoreactive anti-class II T cells in gold salt-triggered B cell polyclonal activation in the Brown-Norway (BN) rat. JASN 3 578 (abstract)... 

Savignac M, Badou B, Delmas C, Subra JF, De Cramer S, Paulet P, Cassar G, Druet P, Saoudi A, Pelletier L. Gold is a T-cell polyclonal activator in BN and LEW rats but favors IL-4 expression only in autoimmune prone BN rats. EurJ Immunol 2001 31 2266-2276. 

PTEN Embryonic lethal In +/- mice t number of activated B cells (polyclonal expansion), t autoantibodies 45 9... 

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. 

The stems of the tree were foimd to contain polysaccharides consisting of arabinose, galactose and galacturonic acid and only minor amoimts of rham-nose. Structural studies indicate that the polymeric material consists of 1,4-linked galacturonic acid residues, terminal, 1,4-, 1,6- and 1,3,6 galactose units and terminal and 1,5-linked arabinofuranose residues. Further studies must be performed on this in order to determine what type of pectin it can be classified as. The Hnkage data indicate that both AG-I and AG-II are present. This polymer was shown to activate polyclonal B-cells [78]. 

PAS Periodic acid-SchiflF reagent PBA Polyclonal B cell activators PBC Primary biliary cirrhosis PBL Peripheral blood lymphocytes PBMC Peripheral blood mononuclear cells PBN N- e f-butyl-a-phenylnitrone PBS Phosphate-buffered saline PC Phosphatidylcholine... 

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-... 

Regarding the cellular phenomenon giving the autoimmune disease in Balb mice, the importance of T cells in the induction of the immune-complex disease was found while in another strain, SJL mice, a polyclonal B cell activation was obtained however, the importance of T cells could not be excluded [209],... 

Assays such as this that use polyclonal mitogens for activation may not be as sensitive as specific antigen-driven systems (Luster et al., 1988). In addition, suppression of the mitogen response does not always correlate with the PFC response. Since mitogenesis represents only a small aspect of B-cell function and maturation, this endpoint is not sensitive to early events that may affect activation, or later events that may affect differentiation of B cells into antibody-secreting cells (Klaus and Hawrylowicz, 1984). 

Klinman, D. M., and Steinberg, A. D., Systemic autoimmune disease arises from polyclonal B cell activation. J. Exp. Med. 165,1755-1760 (1987). 

SLE is a systemic autoimmune disorder characterized by the activation of T and polyclonal B lymphocytes, production of autoantibodies, and formation of immune complexes causing tissue and organ damage (A9). Abnormal Th cytokines are involved in the pathogenesis of autoimmune diseases (H15). Recent reports indicated that peripheral blood mononuclear cells of SLE patients show decreased in vitro production of Thl cytokines IL-2, IFN-y (F8), TNF-a (H14), and IL-12 (H13, L14, L15) with upregulation of Th2 cytokine IL-4 (F8) and IL-10 (L14). Such an imbalance of Th cytokines may account for the polyclonal B cell activation observed in SLE. An earlier report suggested that there was no relationship between in vitro production of Thl and Th2 cytokines and disease activity (B4), whereas other studies demonstrated that serum concentrations of Thl cytokines IL-12 (T6), TNF-a (D4), and IFN-y (A6) are significantly elevated in SLE patients. 

Rheumatoid factors of the IgM and IgG classes have been shown to form immune complexes in serum or joint fluid either by self-association (K17, M4, M26, P13, Sll, W21) or by reaction with native IgG (C4, K17, M4, N5, Sll, W21, W22), and these appear to be the predominant immune complex material in rheumatoid arthritis (C4, Gl, K17, M4, M26, N5, Sll, W21, W22). The primary cause of rheumatoid factor production in rheumatoid arthritis is unknown. However, rheumatoid factors are known to be present in other diseases associated with chronic antigenic stimulation (C14, M14) and can be induced in vitro by stimulation with antigens, autologous aggregated IgG, anti-idiotype reagents, and polyclonal B cell activators such as lipopolysaccharide and Epstein-Barr virus (C4, Dll, F6, F7, Gil, 16, P10, S24). Rheumatoid factors, including IgG rheumatoid factors which form selfassociating intermediate-sized (11-19 S) complexes, play a major role in... 

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