CpG oligodeoxynucleotides stimulate cord blood mononuclear cells to produce immunoglobulins

Landers, Cheri; Bondada, Subbarao

doi:10.1016/j.clim.2005.04.013

Cited by 20 publications

(13 citation statements)

References 41 publications

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“…The majority of plasma cells derived from CD27 Ϫ precursors had germ-line heavy chain variable region gene sequences, excluding the possibility of selective expansion by contaminating CD27 ϩ precursors. These results are consistent with recent studies that demonstrated CpG-induced proliferation in CD27 Ϫ cord blood B cells 32,33 and others showing that CpG stimulation drives naive B cells into IgM-producing plasmablasts. 6 Our results and those of others suggest that CD27 Ϫ B cells have low-level constitutive expression of intracellular TLR-9, with a positive-feedback mechanism to up-regulate protein expression after CpG stimulation.…”

Section: Discussionsupporting

confidence: 83%

CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

Huggins¹,

Pellegrin²,

Felgar³

et al. 2006

Blood

132

138

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Unmethylated CpG DNA activation of naive CD27 ؊ B cells has been reported to require B-cell-receptor (BCR) cross-linking. We describe a culture system using CpG DNA with sequential steps for T-cell-independent activation of naive CD19 ؉ CD27 ؊ human peripheral blood B cells that induces efficient CD138 ؉ plasma-cell differentiation. CD27 ؉ and CD27 ؊ B cells were cultured in a 3-step system: (1)

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Section: Discussionsupporting

confidence: 83%

CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

Huggins¹,

Pellegrin²,

Felgar³

et al. 2006

Blood

132

138

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“…When stimulating cord-blood cells, we observed IgM production, as shown previously (38). At the same time, no IgG was produced and we showed that differentiation into PB/PC was absent.…”

Section: Discussionsupporting

confidence: 60%

Identification of B Cell Defects Using Age-Defined Reference Ranges for In Vivo and In Vitro B Cell Differentiation

Kerk

Jansen

Berge

et al. 2013

The Journal of Immunology

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Primary immunodeficiencies consist to a large extent of B cell defects, as indicated by inadequate Ab levels or response upon immunization. Many B cell defects have not yet been well characterized. Our objective was to create reliable in vivo and in vitro assays to routinely analyze human B cell differentiation, proliferation, and Ig production and to define reference ranges for different age categories. The in vitro assays were applied to classify the developmental and/or functional B cell defects in patients previously diagnosed with common variable immunodeficiency. Apart from standard immunophenotyping of circulating human B cell subsets, an in vitro CFSE dilution assay was used for the assessment of proliferative capacity comparing T cell–dependent and T cell–independent B cell activation. Plasmablast/plasma cell differentiation was assessed by staining for CD20, CD38, and CD138, and measurement of in vitro Ig secretion. At young age, B cells proliferate upon in vitro activation, but neither differentiate nor produce IgG. These latter functions reached adult levels at 5 and 10 y of age for T cell–dependent versus T cell–independent stimulations, respectively. The capacity of B cells to differentiate into plasmablasts and to produce IgG appeared to be contained within the switched memory B cell pool. Using these assays, we could categorize common variable immunodeficiency patients into subgroups and identified a class-switch recombination defect caused by an UNG mutation in one of the patients. We defined age-related reference ranges for human B cell differentiation. Our findings indicate that in vivo B cell functionality can be tested in vitro and helps to diagnose suspected B cell defects.

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“…Impurity of CD27 + cells in these assays is unlikely to account for the differences observed, as the level of CD27 + B cells was slightly higher for the newborn B cell isolates, and did not correlate with the percentage of IgG-secreting cells. Previous reports have demonstrated impaired IgG and IgA secretion in vitro by newborn total B cells relative to adult total B cells following CpG stimulation 37 , or dual pokeweed mitogen (PWM)/donor CD4 T cell stimulation, 38 although comparisons were among total B cell fractions, and adult samples would have contained significantly more memory B cells. We detected no differences in CD40 expression between newborn and adult B cells (data not shown), in agreement with other studies.…”

Section: Discussionmentioning

confidence: 98%

“…Secondly, naive B cells from newborns contain more immature or transitional (CD24 hi /CD38 hi ) B cells than adult naïve B cells, 16 such that differences would be expected when directly comparing newborn and adult naïve B cells. Our approach was selected in order to further characterize neonatal B cells, including functional TLR expression, in the context of prior work, 14, 15, 42 and to model neonatal naïve B cell responses to TLR agonists that may serve as vaccine adjuvants, 43, 44 as any of the neonatal naïve B cell subsets may respond, and indeed may affect one another. Indeed, the differences we report, including robust neonatal naïve B cell functional expression of TLR9, were not predictable from the relative proportion of immature B cells.…”

Section: Discussionmentioning

confidence: 99%

Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells

Pettengill

Haren

et al. 2016

Innate Immun

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Neonatal innate immunity is distinct from that of adults, which may contribute to increased susceptibility to infection and limit vaccine responses. B cells play critical roles in protection from infection and detect PAMPs via TLRs, that, when co-activated with CD40, can drive B cell proliferation and antibody production. We characterized the expression of TLRs in circulating B cells from newborns and adults, and evaluated TLR- and CD40-mediated naïve B cell class-switch recombination (CSR) and cytokine production. Gene expression levels of most TLRs was similar between newborn and adult B cells, except newborn naïve B cells expressed more TLR9 than adult naïve B cells. Neonatal naïve B cells demonstrated impaired TLR2- and TLR7- but enhanced TLR9-mediated cytokine production. Significantly fewer newborn naïve B cells underwent CSR to produce IgG, an impairment also noted with IL-21 stimulation. Additionally, co-stimulation via CD40 and TLRs induced greater cytokine production in adult B cells. Thus, while newborn naïve B cells demonstrate adult-level expression of TLRs and CD40, the responses to stimulation of these receptors are distinct. Relatively high expression of TLR9 and impaired CD40-mediated Ig secretion contributes to distinct innate and adaptive immunity of human newborns and may inform novel approaches to early life immunization.

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CpG oligodeoxynucleotides stimulate cord blood mononuclear cells to produce immunoglobulins

Cited by 20 publications

References 41 publications

CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

CpG DNA activation and plasma-cell differentiation of CD27− naive human B cells

Identification of B Cell Defects Using Age-Defined Reference Ranges for In Vivo and In Vitro B Cell Differentiation

Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells

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