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Arijita Jash, Yinan Wang, Florian J Weisel, Christopher D Scharer, Jeremy M Boss, Mark J Shlomchik, Deepta Bhattacharya
Memory B cell responses are more rapid and of greater magnitude than are primary Ab responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of Ab recall responses. ZBTB32 is highly expressed by mouse and human memory B cells but not by their naive counterparts. Zbtb32(-/-) mice mount normal primary Ab responses to T-dependent Ags. However, Zbtb32(-/-) memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Arvind Shakya, Alon Goren, Alex Shalek, Cody N German, Jeremy Snook, Vijay K Kuchroo, Nir Yosef, Raymond C Chan, Aviv Regev, Matthew A Williams, Dean Tantin
Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4(+) memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter...
November 16, 2015: Journal of Experimental Medicine
Aimee M Beaulieu, Sharline Madera, Joseph C Sun
Immunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells have traditionally been classified as a component of the innate immune system, they have recently been shown in mice and humans to exhibit certain features of immunological memory, including an ability to undergo a clonal-like expansion during virus infection, generate long-lived progeny (i.e. memory cells), and mediate recall responses against previously encountered pathogens--all characteristics previously ascribed only to adaptive immune responses by B and T cells in mammals...
2015: Advances in Experimental Medicine and Biology
Jeffrey D Price, Chie Hotta-Iwamura, Yongge Zhao, Nicole M Beauchamp, Kristin V Tarbell
During autoimmunity, the normal ability of dendritic cells (DCs) to induce T-cell tolerance is disrupted; therefore, autoimmune disease therapies based on cell types and molecular pathways that elicit tolerance in the steady state may not be effective. To determine which DC subsets induce tolerance in the context of chronic autoimmunity, we used chimeric antibodies specific for DC inhibitory receptor 2 (DCIR2) or DEC-205 to target self-antigen to CD11b(+) (cDC2) DCs and CD8(+) (cDC1) DCs, respectively, in autoimmune-prone nonobese diabetic (NOD) mice...
October 2015: Diabetes
Chunlong Zhang, Hongyan Zhao, Jie Li, Hongbo Liu, Fang Wang, Yanjun Wei, Jianzhong Su, Dongwei Zhang, Tiefu Liu, Yan Zhang
Abnormal DNA methylation is known as playing an important role in the tumorgenesis. It is helpful for distinguishing the specificity of diagnosis and therapeutic targets for cancers based on characteristics of DNA methylation patterns across cancers. High throughput DNA methylation analysis provides the possibility to comprehensively filter the epigenetics diversity across various cancers. We integrated whole-genome methylation data detected in 798 samples from seven cancers. The hierarchical clustering revealed the existence of cancer-specific methylation pattern...
2015: PloS One
Aimee M Beaulieu, Carolyn L Zawislak, Toshinori Nakayama, Joseph C Sun
Natural killer (NK) cells are innate lymphocytes that exhibit many features of adaptive immunity, including clonal proliferation and long-lived memory. Here we demonstrate that the BTB-ZF transcription factor Zbtb32 (also known as ROG, FAZF, TZFP and PLZP) was essential for the proliferative burst and protective capacity of virus-specific NK cells. Signals from proinflammatory cytokines were both necessary and sufficient to induce high expression of Zbtb32 in NK cells. Zbtb32 facilitated NK cell proliferation during infection by antagonizing the anti-proliferative factor Blimp-1 (Prdm1)...
June 2014: Nature Immunology
Gwan Gyu Song, Jae-Hoon Kim, Young Ho Lee
The aims of this study were: (1) to identify candidate single-nucleotide polymorphisms (SNPs) and mechanisms of major depressive disorder (MDD) and (2) to generate SNP-to-gene-to-pathway hypotheses. An MDD genome-wide association study (GWAS) data set that included 365,419 SNPs in 1,821 MDD cases and 1,822 controls of European descent was used in this study. Identify Candidate Causal SNPs and Pathway (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 21 candidate SNPs, 16 genes, and 5 pathways, which provided 16 hypothetical biological mechanisms...
October 2013: Journal of Molecular Neuroscience: MN
Matthew A Care, Sharon Barrans, Lisa Worrillow, Andrew Jack, David R Westhead, Reuben M Tooze
Cell of origin classification of diffuse large B-cell lymphoma (DLBCL) identifies subsets with biological and clinical significance. Despite the established nature of the classification existing studies display variability in classifier implementation, and a comparative analysis across multiple data sets is lacking. Here we describe the validation of a cell of origin classifier for DLBCL, based on balanced voting between 4 machine-learning tools: the DLBCL automatic classifier (DAC). This shows superior survival separation for assigned Activated B-cell (ABC) and Germinal Center B-cell (GCB) DLBCL classes relative to a range of other classifiers...
2013: PloS One
Hye Suk Yoon, Christopher D Scharer, Parimal Majumder, Carl W Davis, Royce Butler, Wendy Zinzow-Kramer, Ioanna Skountzou, Dimitrios G Koutsonanos, Rafi Ahmed, Jeremy M Boss
CIITA and MHC class II expression is silenced during the differentiation of B cells to plasma cells. When B cell differentiation is carried out ex vivo, CIITA silencing occurs rapidly, but the factors contributing to this event are not known. ZBTB32, also known as repressor of GATA3, was identified as an early repressor of CIITA in an ex vivo plasma cell differentiation model. ZBTB32 activity occurred at a time when B lymphocyte-induced maturation protein-1 (Blimp-1), the regulator of plasma cell fate and suppressor of CIITA, was minimally induced...
September 1, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
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