TLR9 stimulation of B-cells induces transcription of p53 and prevents spontaneous and irradiation-induced cell death independent of DNA damage responses. Implications for Common variable immunodeficiency

AbstractWe recently showed that when a low X-ray dose is used, cell death is enhanced in nucleus-irradiated compared with whole-cell-irradiated cells; however, the role of the cytoplasm remains unclear. Here, we show changes in the DNA damage responses with or without X-ray microbeam irradiation of the cytoplasm. Phosphorylated histone H2AX foci, a surrogate marker for DNA double-strand breaks, in V79 and WI-38 cells are not observed in nucleus irradiations at ≤ 2 Gy, whereas they are observed in whole-cell irradiations. Addition of an ataxia telangiectasia mutated (ATM) kinase inhibitor to whole-cell irradiations suppresses foci formation at ≤ 2 Gy. ABL1 and p73 expression is upregulated following nucleus irradiation, suggesting the induction of p73-dependent cell death. Furthermore, CDKN1A (p21) is upregulated following whole-cell irradiation, indicating the induction of cell cycle arrest. These data reveal that cytoplasmic radioresponses modify ATM-mediated DNA damage responses and determine the fate of cells irradiated at low doses.

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Failure of B cells in common variable immunodeficiency to transit from proliferation to differentiation is associated with altered B cell surface-molecule display

Journal of Allergy and Clinical Immunology ◽

10.1016/0091-6749(89)90177-2 ◽

1989 ◽

Vol 84 (1) ◽

pp. 44-55 ◽

Cited By ~ 18

Author(s):

A SAXON ◽

J GIORGI ◽

E SHERR ◽

J KAGAN

Keyword(s):

B Cells ◽

Cell Surface ◽

B Cell ◽

Common Variable Immunodeficiency ◽

Surface Molecule ◽

Cell Surface Molecule ◽

Common Variable

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Phenotypic Comparison of B cells in Discordant Identical Twins with Common Variable Immunodeficiency and Recurrent Sino-Pulmonary Infection Patients

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2011.12.350 ◽

2012 ◽

Vol 129 (2) ◽

pp. AB157

Author(s):

T.A. Hwangpo ◽

E. Szymanska ◽

C.R. Liu ◽

M.G. Brand ◽

E.E. Brown ◽

...

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Pulmonary Infection ◽

Identical Twins ◽

Common Variable

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Common Variable Immunodeficiency / Cvid

Journal of Clinical Review & Case Reports ◽

10.33140/jcrc/03/02/00001 ◽

2018 ◽

Vol 3 (2) ◽

Keyword(s):

B Cells ◽

Common Variable Immunodeficiency ◽

Autoimmune Disorders ◽

Common Variable

“Variable” refers to the heterogeneousclinicalmanifestations of thisdisorder, which can include: recurrentinfections, chroniclungdisease, autoimmune disorders, also involve varioussegments of the gastrointestinaltract and a heightenedsusceptibility to lymphoma. Itis a primaryimmunodeficiencythataffects 1 in 50,000 peopleworldwide. Itischaracterized by reducedimmunoglobulinserumlevels and absent or impairedantibody production. The pathogenic of CVID isnotknown; however, therehavebeennumerousassociatedlaboratoryfindingsincludingnumerousmutations in the genesresult in dysfunctional B cells. The mostfrequentmutationsoccur in the TNFRSF13B gene. Genesthathavebeenimplicated in monogenic CVID include ICOS, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), TNFRSF7 (CD27), IL21, IL21R, LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R1, VAV1, RAC2, BLK, IKZF1 (IKAROS) and IRF2BP2 [1]. In addition, thereisevidence of complexinheritanceratherthan a monogenic CVID.

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