Retinoic acid and α-galactosylceramide regulate the expression of costimulatory receptors and transcription factors responsible for B cell activation and differentiation

Chen, Qiuyan; Mosovsky, Kara L.; Ross, A. Catharine

doi:10.1016/j.imbio.2013.05.003

Cited by 15 publications

(18 citation statements)

References 51 publications

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“…Since B cells are APC and the expression of CD1d is upregulated by RA (Chen et al, 2013), B cell differentiation was also examined after this treatment (Fig. 5F).…”

Section: Resultsmentioning

confidence: 99%

“…As an antigen-presenting molecule, CD1d is closely related to the activity of NKT cells and B cells (Chen et al, 2013; Rossjohn et al, 2012). Thus, the expression and distribution of CD1d may be an important regulator of the downstream immune responses of these cells, such as cytokine and antibody production.…”

Section: Discussionmentioning

confidence: 99%

“…Only recently have B cells been studied as carriers of the CD1d molecule, and these studies have demonstrated a close interaction between NKT cells and B cells during humoral immune responses (Allan et al, 2011; Bai et al, 2013). It is known that both RA and CD38 ligation can induce B cell differentiation (Chen and Ross, 2005), and it is especially interesting that RA also increased B cell CD1d expression (Allan et al, 2011; Chen et al, 2013). The increase in B cells having germinal center B cell characteristics by RA and CD38 ligation, especially in the presence of αGalCer, suggests that RA and CD38 signaling are involved in CD1d/αGalCer-mediated B cell activation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

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All-trans-retinoic acid and CD38 ligation differentially regulate CD1d expression and α-galactosylceramide-induced immune responses

Chen

Ross

2015

Immunobiology

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The MHC class-I like molecule CD1d presents glycolipid antigens and thereby activates invariant natural killer-T (NKT) cells. However, little is understood regarding the regulation of its expression. All-trans-retinoic acid (RA) and CD38, which is itself a target of RA, both independently regulate the differentiation of antigen presenting cells. In the current study, we treated human THP-1 cells and murine splenic cells with RA, with and without antibody-mediated ligation of cell-surface CD38. Whereas a physiological concentration (20 nM) of RA alone rapidly and markedly increased CD1d protein in THP-1 cells, there was a marked synergy between RA and ligation of CD38 with antibody to CD38. Moreover, RA and CD38 ligation differentially regulated CD1d protein distribution between the cell surface and intracellular compartments, as, whereas RA mainly increased intracellular CD1d protein, ligation of CD38 increased CD1d protein both at the cell surface and intracellularly. By confocal microscopy, CD1d was located close to the plasma membrane but only partially overlapped with LAMP1, a late endosomes/lysosomal marker. Furthermore, RA and/or CD38 ligation increased splenocyte proliferation and differentiation after treatment with the CD1 ligand α-galactosylceramide (αGalCer), evidenced by an increase in the number of splenic dendritic cells, NKT cells, and germinal center plasmacytes. RA also differentially regulated αGalCer-induced cytokine expression, increasing IL-4 and decreasing IFNγ production by total spleen cells and the NKT cell population. Our results indicate a previously unknown mechanism in which RA and CD38 differentially yet cooperatively regulate CD1d expression and antigen-presenting function, which could be important for the enhancement of immunity.

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“…Since B cells are APC and the expression of CD1d is upregulated by RA (Chen et al, 2013), B cell differentiation was also examined after this treatment (Fig. 5F).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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All-trans-retinoic acid and CD38 ligation differentially regulate CD1d expression and α-galactosylceramide-induced immune responses

Chen

Ross

2015

Immunobiology

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“…In addition, retinoic acid induces isotype switching to IgA [80,81] and retinoic acid signaling in B cells has been shown to be essential for induction of antigen-specific high-affinity sIgA responses after oral immunization [82]. Several studies have demonstrated a positive effect of retinoic acid as an adjuvant for vaccination against mucosal infections [82][83][84].…”

Section: The Requirement For Oral Adjuvantsmentioning

confidence: 99%

What Makes A Bacterial Oral Vaccine a Strong Inducer of High-Affinity IgA Responses?

Moor

Slack

2015

Antibodies

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Abstract:Oral vaccination against bacterial pathogens that infect via the gastrointestinal tract is highly desirable for both economic reasons and the supposed benefits of local mucosal immunity. However, the majority of oral vaccine trials in humans result in failure. Here we try to assimilate our current knowledge to generate a model to improve vaccine development strategies. A model previously postulated describes the "immunogenicity" of intestinal bacterial species as a sum of the ability of the species to compete with the microbiota, the "pathogenicity index," and the uniqueness of the species. While this model quite neatly explains the difficulties in generating appropriately attenuated live vaccine strains, it cannot explain the success of fully apathogenic or inactivated high-dose vaccines. We therefore propose a step away from focusing on bacterial traits, and towards the most basic requirements of mucosal vaccines: i.e., the delivery of antigen to the gut-associated lymphoid tissues and the ability of that antigen to induce germinal center formation. While the models seem trivial, both suggest that vaccination strategies permitting uncoupling of disease-causing phenomena from immune stimulation will have a much broader safety margin in a diverse human population. Our modified model further suggests the benefits of delivering antigen in the form of high-dose fully apathogenic or sterile particles, combined with relevant adjuvants. OPEN ACCESSAntibodies 2015, 4 296

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“…The underlying mechanisms by which αGalCer works are centred mainly on the rapid activation of CD1d-restricted invariant natural killer (NK) T cells (iNK T) [19] which, upon stimulation, produce significant amounts of both interferon (IFN)-γ and interleukin (IL)-4 which then, in turn, influence the differentiation of dendritic cells, stimulation of macrophages to produce IL-12 and activation of T and B cells [20][21][22]. Previously, we have shown that αGalCer is a strong stimulator for B cells of the adult mouse [23,24]. αGalCer induced B cell proliferation and differentiation to increase the number of antibody-secreting cells in vitro and increased the production of tetanus toxoid (TT)-specific antibodies in vivo.…”

Section: Introductionmentioning

confidence: 99%

α-Galactosylceramide stimulates splenic lymphocyte proliferation in vitro and increases antibody production in vivo in late neonatal-age mice

Chen

Ross

2015

Clinical and Experimental Immunology

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SummaryThe neonatal stage is characterized by weak responses to various infections and vaccines, thus the development of efficient formulas to improve vaccine effectiveness is of high priority. The glycolipid alpha galactosylceramide (αGalCer) is known as a potent immune modulator due mainly to natural killer (NK) T cell activation. Using a mouse tetanus toxoid (TT) immunization model, we observed that neonatal mice given αGalCer at the time of primary immunization on postnatal day (pnd) 17 had a significantly higher TT-specific immunoglobulin (Ig)M response as well as a memory IgG response, while αGalCer given on pnd 7 resulted in only marginal boosting. Consistently, immunostaining of the spleen sections from αGalCer-treated pnd 17 immunized neonates showed a higher number of Ki67 + cells in the splenic germinal centre area, suggesting a stronger response after immunization. In-vitro kinetic studies revealed that spleen cells from newborn to pnd 7 neonates did not respond to αGalCer stimulation, whereas cell proliferation was increased markedly by αGalCer after pnd 7, and became dramatic around neonatal pnd 17-18, which was accompanied by increased B, T and NK T cell populations in the spleen. In addition, in pnd 17 spleen cells, αGalCer significantly stimulated the production of NK T cytokines, interleukin (IL)-4 and interferon (IFN)-γ, and promoted the proliferation of CD23 + B cells, a subset of B cells enriched in germinal centres. These data suggest that αGalCer is an effective immune stimulus in the late neonatal stage, and thus may be useful in translational studies to test as a potential adjuvant to achieve a more efficient response to immunization.

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Retinoic acid and α-galactosylceramide regulate the expression of costimulatory receptors and transcription factors responsible for B cell activation and differentiation

Cited by 15 publications

References 51 publications

All-trans-retinoic acid and CD38 ligation differentially regulate CD1d expression and α-galactosylceramide-induced immune responses

All-trans-retinoic acid and CD38 ligation differentially regulate CD1d expression and α-galactosylceramide-induced immune responses

What Makes A Bacterial Oral Vaccine a Strong Inducer of High-Affinity IgA Responses?

α-Galactosylceramide stimulates splenic lymphocyte proliferation in vitro and increases antibody production in vivo in late neonatal-age mice

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