Differentiation factors for human specific B cell response

Vázquez, Aimé; Gerard, J. -P.; Delfraissy, Jean‐François; Dugas, Bernard; Auffredou, Marie Thérèse; Crevon, Marie‐Claude; Fradelizi, D; Galanaud, Pierre

doi:10.1002/eji.1830160714

Cited by 12 publications

(5 citation statements)

References 38 publications

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“…We have previously shown [13,191 that TNP-PAA beads deliver to the B cells an early and specific signal independently of T cell help. This allowed us to examine whether IL4 was counteracting the effect of IL2 after B cells had been activated through membrane Ig.…”

Section: Discussionmentioning

confidence: 99%

Interleukin (IL) 4 counteracts the helper effect of IL 2 on antigen‐activated human B cells

et al. 1989

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We tested the effect of interleukin (IL) 4 on the specific IgM antibody response induced by trinitrophenylated-polyacrylamide beads (TNP-PAA) in cultures of human B cells. T cell help was provided by exogeneous IL2. IL4 profoundly suppressed the response to optimal concentrations (50 U/ml) of IL2, with a 50% inhibitory concentration of 6 U/ml. This was due neither to a shift in the kinetics nor to a switch to an IgG response. The production of anti-TNP antibody (as measured by an enzyme-linked immunosorbent assay in the culture supernatant) was inhibited to the same extent as the generation of plaque-forming cells. The effect of IL4 was completely abolished by a neutralizing antibody toward IL4. Kinetic studies showed that IL4 had to be present during the first 48 h of culture to fully inhibit the response. The sequential stimulation of B cells by antigen and by IL2 showed that IL4 does not negatively interfere with signaling through membrane Ig but counteracts the effect of IL2 on antigen-activated B cells.

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Section: Discussionmentioning

confidence: 99%

Interleukin (IL) 4 counteracts the helper effect of IL 2 on antigen‐activated human B cells

et al. 1989

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“…In our original study [6], TRF activity in PHA-CM was found in a 35-kDa fraction and was reduced but not eliminated by absorption with an IL2-dependent T cell line. Vazquez et al [15] have also described aTRF in PHA-CM which was distinct from IL 2.…”

Section: Discussionmentioning

confidence: 93%

“…CM from PHA-activated T cells will replace Th cells in specific antibody responses by human blood or tonsillar B cells toT-dependent antigens such as influenza virus [6] and TNP-PAA [15]. PHA-CM contains many factors which act on B cells, and there are conflicting reports about the nature of the TRF in these preparations.…”

Section: Discussionmentioning

confidence: 99%

Human t cell-replacing factor(s): a comparison of recombinant and purified human b cell growth and differentiation factors

1989

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Conditioned medium from phytohemagglutinin-activated T cells contains T cell-replacing factor(s) (TRF) able to restore specific antibody responses by human blood or tonsillar B cells which have been thoroughly depleted of T cells. Of twelve recombinant cytokines tested as possible candidates for TRF in conditioned media, namely human recombinant interleukin (hrIL) 1 alpha and beta, hrIL2, hrIL3, hrIL4, hrIL5, hrIL6, hrIFN-alpha and -gamma, hr granulocyte macrophage colony-stimulating factor (hrGM-CSF) and tumor necrosis factor (hr TNF)-alpha and -beta only IL2 was found to have TRF activity. In addition, a semi-purified low molecular weight B cell growth factor (BCGFlow) also had TRF activity. As the commercially available BCGFlow is known to contain low concentrations of IL2, IFN-gamma, TNF and GM-CSF as impurities, it was important to exclude these as being responsible for the TRF activity. At the concentrations present in BCGFlow (less than 0.2 U/ml), IL2 was not active in the TRF assay. In contrast, a combination of IL2 (0.2 U/ml), IFN-gamma (50 U/ml), TNF-alpha (50 U/ml) and TNF-beta (100 U/ml) did have TRF activity suggesting that B cells could be made to respond to low doses of IL2 by the presence of other cytokines. Although this finding raises important questions about the nature of TRF in conditioned medium, the TRF activity of BCGFlow was unlikely to be due to such a synergistic combination of cytokines for the following reasons. First, in several experiments, responses were obtained with BCGFlow, but not with IL2 or combinations of IL2 with IFN and TNF. Second, antibody to IL2 was found to inhibit the TRF activity of IL2 but not of BCGFlow. Taken together these findings show that two distinct cytokines (IL2 and BCGFlow) are TRF for human B cells. However, some combinations of cytokines can also have TRF activity underlining the complexities which can arise from working with semi-purified rather than recombinant factors.

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“…We used a semipurified T supernatant (TSN) [16]. B-enriched cells (lo6/ culture well) were cultured as described above for PBL, in the presence or absence of TSN.…”

Section: Specific Antibody Response Of B-enriched Cellsmentioning

confidence: 99%

Regulation of human B cell activation and antibody production by non‐major histocompatibility complex‐restricted cytotoxic T lymphocytes

et al. 1989

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To determine whether non-major histocompatibility complex-restricted cytotoxic human T lymphocytes (NrCTL) are involved in the regulation of antibody response, we studied the effect of a CD3+, T cell receptor (TcR)-alpha/beta+, NKH1+ clone named JT9 on B cell proliferation and differentiation. It was found that low amounts of JT9 clone (5%) profoundly inhibited (greater than 80%) in vitro specific anti-trinitrophenyl primary antibody response. This inhibition did not need the presence of autologous T cells and took place at the induction phase of the antibody response. JT9 clone had no effect on resting B cells but enhanced proliferation of anti-mu-stimulated B cells. Respective involvements of cell to cell interaction, cytotoxicity and lymphokines were investigated. (a) The effect of monoclonal antibodies (mAb) inhibiting cytotoxic properties of JT9 clone, i.e. an anti-clonotypic structure mAb and a mAb directed against a target cell antigen similar to 4F2, were studied. These mAb did not reverse the effects of JT9 on B cell activation and differentiation. Thus, these contrasting effects of JT9 clone on B cell response did not seem to involve an interaction of JT9 clone TcR with its target or, further, cytotoxic properties for which this clone had been characterized. (b) Supernatant of JT9 clone stimulated by cross-linking of TcR complex, in the absence of interleukin 2, exerted a proliferative effect on anti-mu-stimulated B cells but not on resting B cells. These findings suggest that JT9 clone could secrete a B cell growth factor-like activity and that NrCTL cells may play an important role in the regulation of antibody response.

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Differentiation factors for human specific B cell response

Cited by 12 publications

References 38 publications

Interleukin (IL) 4 counteracts the helper effect of IL 2 on antigen‐activated human B cells

Interleukin (IL) 4 counteracts the helper effect of IL 2 on antigen‐activated human B cells

Human t cell-replacing factor(s): a comparison of recombinant and purified human b cell growth and differentiation factors

Regulation of human B cell activation and antibody production by non‐major histocompatibility complex‐restricted cytotoxic T lymphocytes

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