Modulation of B-Cell Immunoglobulin Synthesis by Retinoic Acid

Ballow, Mark; Wang, Weiping; Xiang, Shunan

doi:10.1006/clin.1996.0144

Cited by 38 publications

(27 citation statements)

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“…Further more, supernatant fluids generated from cultures containing purified T cells and RA were able to augment IgM synthesis [1]. In this study, RA increased the relative levels of mRNA by more than 2.5-fold, and in 2 o f 4 experiments RA in creased IL-2 supernatant levels.…”

Section: Discussionsupporting

confidence: 45%

“…These properties range from the pro motion ofT lymphocyte proliferation to augmenting immu noglobulin (Ig) synthesis [1][2][3][4]. Our laboratory has been in terested in the effects of all-/ra«.v-retinoic acid (RA) in aug menting formalin-treated staphylococcus-stimulated B cell Ig production, and the mechanism by which this augmenta tion in Ig synthesis occurs [1,5,6], Both IL-2 and IL-6 are important cytokines for B cell differentiation and Ig secre tion [7], Recent studies in our laboratory suggest that the Ig-augmenting effects of RA is mediated, at least in part, by IL-6 through autocrine or paracrine pathways [8] This article is also accessible online at: http://www.karger.ch http://BioMedNct.com/karger direct effect of RA on T cells [1], We propose that RA can modulate other cytokines, c.g. IL-2, and that this effect may be mediated through specific RA nuclear receptors.…”

Section: Introductionmentioning

confidence: 99%

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Retinoic Acid-Induced Modulation of IL-2 mRNA Production and IL-2 Receptor Expression on T Cells

Ballow

Xiang²,

Greenberg³

et al. 1997

Int Arch Allergy Immunol

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Background: Retinoic acid (RA) has important immune-modulating effects on both T and B cell function. Our laboratory has shown that RA can enhance in vitro polyclonal B cell immunoglobulin (Ig) response. Investigating cytokines known to affect B cell differentiation, we have recently shown that IL-6 production is augmented by RA. In the present study we have examined the immune modulating effects of RA on IL-2 mRNA, another important cytokine for B cell immunoglobulin production, the expression of IL-2 receptors on T cells, and the RA nuclear receptors. Methods: Purified T cells were obtained from adenoidal tissues, and incubated with RA (10^––⁷ M) or DMSO solvent/media control for 0, 6–8, and 24 h. Total mRNA was extracted from T cells, and using RT-PCR, changes in the production of IL-2 and RA receptors (RAR)-αβγ mRNA were determined. The effects of RA on IL-2-α receptor expression was determined by flow cytometry on T cells. Conclusion: These studies suggest that RA can augment IL-2 mRNA production by T cells with a possible paracrine effect on IL-2R-α expression. These changes appear to be mediated by RAR-α. Thus, IL-2 may be another important cytokine modulated by RA in the immune response.

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Section: Discussionsupporting

confidence: 45%

Section: Introductionmentioning

confidence: 99%

Retinoic Acid-Induced Modulation of IL-2 mRNA Production and IL-2 Receptor Expression on T Cells

Ballow

Xiang²,

Greenberg³

et al. 1997

Int Arch Allergy Immunol

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“…The active vitamin A (VA) derivative, retinoic acid (RA), increases thymocyte differentiation 15,16 and enhances the lymphocyte response to mitogens 17–19 . Retinoids have also been shown to stimulate antibody production in vivo and in vitro 20–22 . On the other hand, VA‐deficient mice show a reduced IgG1 and IgG3 response, which is restored by RA 23,24 .…”

Section: Introductionmentioning

confidence: 99%

Retinoid‐ and carotenoid‐enriched diets influence the ontogenesis of the immune system in mice

et al. 2003

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SUMMARYVitamin A (VA) has been identi®ed as an important factor for the development of the immune system, especially during ontogenesis. It has been shown that antibody secretion and proliferation of lymphocyte populations depend on retinoids. In the present study we investigated the in¯uence of a base VA diet and diets enriched with VA, b-carotene and lycopene, on the ontogenesis of the immune system in mice. We examined the absolute and relative concentrations of splenic B lymphocytes (CD45R/B220), T lymphocytes (CD3 ) and their subpopulations (CD4 and CD8 ), and measured serum immunoglobulin G (IgG) concentrations in the offspring of supplemented dams at different ages (1, 3, 5, 7, 14, 21 and 65 days). The experimental diets resulted in higher numbers of T and B lymphocytes after VA and carotenoid enrichment, when compared, at various time-points, with the base diet. Higher values of total serum IgG were found in the b-carotene-enriched diet group on day 7. On days 7 and 14, the enriched diets induced signi®cant alterations in the percentages and total numbers of splenic lymphocytes in comparison to the base diet. Our results con®rm that supplementation with VA and carotenoids affect the immune-cell function during ontogenesis and suggest a possible role of these nutritional factors on the development of the immune system.

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“…[4][5][6][7][8][9][10][11] However, there has been some controversy regarding the importance of vitamin A for B-cell activity. Some reports document that retinoids are required for B-cell activity 12 and have the potential to enhance differentiation and antibody responses of B cells, [13][14][15][16] and that B-cell responses are impaired in vitamin A-deficient rats. 17 We have previously shown that RA inhibits the proliferation of human and murine B-cell precursors 18 as well as peripheral-blood B cells stimulated via B-cell receptor (BcR).…”

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confidence: 99%

Vitamin A potentiates CpG-mediated memory B-cell proliferation and differentiation: involvement of early activation of p38MAPK

Ertesvag

Aasheim

Naderi

et al. 2007

Blood

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Foreign CpG-DNA from viruses and bacteria can activate memory B cells through binding to toll-like receptor 9, and this pathway has been hypothesized to be involved in the continuous activation of memory B cells ensuring life-long humoral immunity. In this study, we demonstrate that retinoic acid (RA) is a potent coactivator of this pathway in human B cells. RA enhanced the CpG-mediated proliferation of CD27 ؉ memory B cells, and the proliferative response was accompanied by increased immunoglobulin (Ig) secretion indicative of plasma-cell formation. The RA-induced proliferation was preceded by enhanced expression of cyclin D3, and both the expression of cyclin D3 and the induced Ig secretion were found to be dependent on IL-10. Of importance, RA increased the CpG-induced phosphorylation of ERK1/2, p38MAPK, and IB as early as 30 minutes after stimulation. By using specific inhibitors, all the RA-mediated events, including proliferation, cyclin D3 expression, IL-10 se- IntroductionVitamin A is important for an optimal functioning of the immune system, but the mechanisms involved are not fully understood. A part of the increased resistance to infection has been attributed to improved epithelial integrity, but a direct effect on cells of the immune system is also established. [1][2][3] We and others have shown that all-trans retinoic acid has a stimulatory role in T lymphocytes. [4][5][6][7][8][9][10][11] However, there has been some controversy regarding the importance of vitamin A for B-cell activity. Some reports document that retinoids are required for B-cell activity 12 and have the potential to enhance differentiation and antibody responses of B cells, [13][14][15][16] and that B-cell responses are impaired in vitamin A-deficient rats. 17 We have previously shown that RA inhibits the proliferation of human and murine B-cell precursors 18 as well as peripheral-blood B cells stimulated via B-cell receptor (BcR). 19 We also demonstrated that the inhibition of B-cell proliferation was accompanied by inhibition of the cell-cycle machinery driving the cells from G 1 to S phase. 20 In the primary immune response, naive B cells proliferate and differentiate into plasma cells that secrete antibodies mainly of the immunoglobulin-M (IgM) class. During this process, somatic hypermutation and isotype switching take place, producing highaffinity antibodies of the IgG class. 21 Some B cells embark on a different program to become long-lived memory B cells, which are characterized by lower threshold for activation and differentiation. 22 In the past 2 decades, it has become clear that B cells can be activated by DNA from bacteria and viruses. 23 The discrimination between human and bacterial/viral DNA is based on the fact that CpG dinucleotides are underrepresented and generally methylated in vertebrate DNA, while they are present at expected frequency and are unmethylated in bacteria and viruses. 23,24 Unmethylated CpG DNA is recognized by toll-like receptor 9 (TLR9), which is primarily expressed in memory B cells and plas...

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Modulation of B-Cell Immunoglobulin Synthesis by Retinoic Acid

Cited by 38 publications

References 0 publications

Retinoic Acid-Induced Modulation of IL-2 mRNA Production and IL-2 Receptor Expression on T Cells

Retinoic Acid-Induced Modulation of IL-2 mRNA Production and IL-2 Receptor Expression on T Cells

Retinoid‐ and carotenoid‐enriched diets influence the ontogenesis of the immune system in mice

Vitamin A potentiates CpG-mediated memory B-cell proliferation and differentiation: involvement of early activation of p38MAPK

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