B-cell memory and primary immune deficiencies

Desjardins, Marylin; Mazer, Bruce

doi:10.1097/aci.0000000000000009

Cited by 20 publications

(13 citation statements)

References 52 publications

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“…A downregulation of IL21R might play a role in the persistence of colonization during the primary E. coli O157:H7-infection and re-infection of the host, since the IL-21-IL-21R pathway is important in the development of immune responses, as abnormal signaling through the IL-21R/γc/JAK3/STAT3 pathway leads to defective humoral immune responses to both T-dependent and T-independent antigens and impairs the establishment of long-lasting B-cell memory [52]. A bacterial infection can elicit IgM memory B-cells which requires T cell- dependent and IL-21R signaling.…”

Section: Discussionmentioning

confidence: 99%

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

Kieckens

Rybarczyk

Li³

et al. 2016

BMC Genomics

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Background: Enterohaemorrhagic Escherichia coli (EHEC), like E. coli O157:H7 are frequently detected in bovine faecal samples at slaughter. Cattle do not show clinical symptoms upon infection, but for humans the consequences after consuming contaminated beef can be severe. The immune response against EHEC in cattle cannot always clear the infection as persistent colonization and shedding in infected animals over a period of months often occurs. In previous infection trials, we observed a primary immune response after infection which was unable to protect cattle from reinfection. These results may reflect a suppression of certain immune pathways, making cattle more prone to persistent colonization after re-infection. To test this, RNA-Seq was used for transcriptome analysis of recto-anal junction tissue and ileal Peyer's patches in nine Holstein-Friesian calves in response to a primary and secondary Escherichia coli O157: H7 infection with the Shiga toxin (Stx) negative NCTC12900 strain. Non-infected calves served as controls. Results: In tissue of the recto-anal junction, only 15 genes were found to be significantly affected by a first infection compared to 1159 genes in the ileal Peyer's patches. Whereas, re-infection significantly changed the expression of 10 and 17 genes in the recto-anal junction tissue and the Peyer's patches, respectively. A significant downregulation of 69 immunostimulatory genes and a significant upregulation of seven immune suppressing genes was observed.

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Section: Discussionmentioning

confidence: 99%

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

Kieckens

Rybarczyk

Li³

et al. 2016

BMC Genomics

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“…Thus B cell receptor (BCR) activation induces B cell apoptosis, even enhanced by IL-21, if survival signals provided through CD40 contact are absent. Accordingly, the stimulatory/inhibitory effect of IL-21 depends on the accompanying signal and the B cell subpopulation evaluated 17 , 18 . We previously demonstrated that memory B cell loss in a CVID patients’ subgroup (with compromised memory B cell compartment) could be the consequence of increased susceptibility to activation-induced apoptosis 15 .…”

Section: Introductionmentioning

confidence: 99%

IL-21 and anti-CD40 restore Bcl-2 family protein imbalance in vitro in low-survival CD27+ B cells from CVID patients

et al. 2018

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Common variable immunodeficiency (CVID) is characterized by an abnormal B cell differentiation to memory and antibody-secreting B cells. The defective functionality of CVID patients’ B cells could be the consequence of alterations in apoptosis regulation. We studied the balance of Bcl-2 family anti-/pro-apoptotic proteins to identify molecular mechanisms that could underlie B cell survival defects in CVID. We used flow cytometry to investigate Bcl-2, Bcl-XL, Bax, and Bim expression in B cells ex vivo and after anti-CD40 or anti-BCR activation with or without IL-21, besides to spontaneous and stimulation-induced Caspase-3 activation and viable/apoptotic B cell subpopulations. We found increased basal levels of Bax and Bim in CVID B cells that correlated with low viability and high Caspase-3 activation only in CD27+ B cells, particularly in a subgroup of apoptosis-prone CVID (AP-CVID) patients with low peripheral B cell counts and high autoimmunity prevalence (mostly cytopenias). We detected a broad B cell defect in CVID regarding Bcl-2 and Bcl-XL induction, irrespective of the stimulus used. Therefore, peripheral CVID memory B cells are prompted to die from apoptosis due to a constitutive Bcl-2 family protein imbalance and defective protection from activation-induced apoptosis. Interestingly, anti-CD40 and IL-21 induced normal and even higher levels of Bcl-XL, respectively, in CD27+ B cells from AP-CVID, which was accompanied by cell viability increase. Thus low-survival memory B cells from AP-CVID can overcome their cell death regulation defects through pro-survival signals provided by T cells. In conclusion, we identify apoptosis regulation defects as disease-contributing factors in CVID. B cell counts and case history of cytopenias might be useful to predict positive responses to therapeutic approaches targeting T-dependent signaling pathways.

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“…Although there is a selective failure of immune tolerance to specific mitochondrial autoantigens in primary biliary cirrhosis (PBC), and systemic evidence of B‐cell dysregulation, there is a paucity of data that provide a mechanistic explanation of these abnormalities of B‐cell immune responses. Clearly, there are multiple factors that regulate B‐cell homeostasis, including activation of B‐cell receptors, interaction with multiple coreceptors, and interactions with the local cytokine microenvironment . The lymphoid microenvironment is particularly critical for B‐cell proliferation and differentiation as well as fulfilling a requirement for establishment of an enduring immune response.…”

mentioning

confidence: 99%

Chemokine (C‐X‐C motif) ligand 13 promotes intrahepatic chemokine (C‐X‐C motif) receptor 5+ lymphocyte homing and aberrant B‐cell immune responses in primary biliary cirrhosis

Wang

Tang

et al. 2015

Hepatology

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The serologic hallmark of primary biliary cirrhosis (PBC) is the presence of high titer, and specific anti-mitochondrial antibodies (AMA). Interestingly, although there is no global immune defect in patients with PBC, there is widespread dysregulated B cell function, including increased sera levels of IgM and enhanced B cell responses to CpG stimulation. The mechanisms involved in this B cell dysfunction have remained unknown. To address this issue, we focused on identifying the frequencies of B cell subsets in patients with PBC and the mechanisms that lead to B cell dysregulation, including the relationships with CXCR5+CD4+T cells. Herein we report that elevations of both serum and intrahepatic IL-21 were found in patients with PBC and, in particular, promoted B cell proliferation, STAT3 phosphorylation and AMA production in vitro. More importantly, upon stimulation with rPDC-E2, CXCR5+CD4+T cells in PBC produced higher levels of IL-21 than healthy controls. Additionally, sorted CXCR5+CD4+T cells increased production of AMA by autologous CD19+B cells. Indeed, elevated expression of intrahepatic CXCL13, a key chemokine of CXCR5+ cells, was uniquely found within the portal tracts in PBC, accompanied by infiltrates of CD4+, CXCR5+, CD19+, and CD38+ cells. In conclusion, CXCL13 promotes aggregation of CD19+B cells and CXCR5+CD4+T cells, which directs the aberrant AMA response via IL-21. These data have implications for potential immunotherapy and also reflect the unique lymphoid biology in the liver of PBC.

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B-cell memory and primary immune deficiencies

Cited by 20 publications

References 52 publications

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

IL-21 and anti-CD40 restore Bcl-2 family protein imbalance in vitro in low-survival CD27+ B cells from CVID patients

Chemokine (C‐X‐C motif) ligand 13 promotes intrahepatic chemokine (C‐X‐C motif) receptor 5+ lymphocyte homing and aberrant B‐cell immune responses in primary biliary cirrhosis

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