8 research outputs found

    Salivary Gland Mucosa-Associated Lymphoid Tissue-Type Lymphoma From Sjogren's Syndrome Patients in the Majority Express Rheumatoid Factors Affinity-Selected for IgG

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    Objective: Patients with Sjӧgren's syndrome (SS) have an increased risk of developing malignant B cell lymphomas, particularly mucosa-associated lymphoid tissue (MALT)–type lymphomas. We have previously shown that a predominant proportion of patients with SS-associated salivary gland MALT lymphoma express somatically hypermutated IgM with strong amino acid sequence homology with stereotypic rheumatoid factors (RFs). The present study was undertaken in a larger cohort of patients with SS-associated MALT lymphoma to more firmly assess the frequency of RF reactivity and the significance of somatic IGV-region mutations for RF reactivity. Methods: B cell antigen receptors (BCRs) of 16 patients with SS-associated salivary gland MALT lymphoma were analyzed. Soluble recombinant IgM was produced of 12 MALT lymphoma samples, including 1 MALT lymphoma sample that expressed an IgM antibody fitting in a novel IGHV3-30–encoded stereotypic IGHV subset. For 4 of the 12 IgM antibodies from MALT lymphoma samples, the somatically mutated IGHV and IGKV gene sequences were reverted to germline configurations. Their RF activity and binding affinity were determined by enzyme-linked immunosorbent assay and surface plasmon resonance, respectively. Results: Nine (75%) of the 12 IgM antibodies identified in patients with SS-associated salivary gland MALT lymphoma displayed strong monoreactive RF activity. Reversion of the IGHV and IGKV mutations to germline configuration resulted in RF affinities for IgG that were significantly lower for 3 of the 4 somatically mutated IgM antibodies. In stereotypic IGHV3-7/IGKV3-15–encoded RFs, a recurrent replacement mutation in the IGKV3-15–third complementarity-determining region was found to play a pivotal role in the affinity for IgG-Fc. Conclusion: A majority of patients with SS-associated salivary gland MALT lymphoma express somatically mutated BCRs that are selected for monoreactive, high-affinity binding of IgG-Fc. These data underscore the notion that soluble IgG, most likely in immune complexes in inflamed tissues, is the principal autoantigen in the pathogenesis of a variety of B cell lymphomas, particularly SS-associated MALT lymphomas

    Een typologie van jonge nieuwsgebruikers in een multimediaal landschap

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    How to take advantage of tablet computers: Effects of news structure on recall and comprehension

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    © 2015 Walter de Gruyter GmbH, Berlin Boston. In light of the growing use of tablets for news reading and mobile news consumption behaviors, this study examined whether an innovative way of structuring news on the tablet that mimics mobile news behaviors reinforced attention for, and learning from, news. Specifically, it was theorized that the chronological and associative structuring of news articles into so-called developing news stories would lead to more attention for news, and better recall and comprehension of news, than the linear print newspaper structure that newspaper publishers continue to copy from print to tablet. A multiple-day experiment was set up using the eye-tracking method to measure and control for attention. The results show that the developing news structure increased comprehension of news substantively, independently of attention effects; no effects were found on attention and factual recall.status: publishe

    How to take advantage of tablet computers:Effects of news structure on recall and comprehension

    Get PDF
    In light of the growing use of tablets for news reading and mobile news consumption behaviors, this study examined whether an innovative way of structuring news on the tablet that mimics mobile news behaviors reinforced attention for, and learning from, news. Specifically, it was theorized that the chronological and associative structuring of news articles into so-called developing news stories would lead to more attention for news, and better recall and comprehension of news, than the linear print newspaper structure that newspaper publishers continue to copy from print to tablet. A multiple-day experiment was set up using the eye-tracking method to measure and control for attention. The results show that the developing news structure increased comprehension of news substantively, independently of attention effects; no effects were found on attention and factual recall

    Conserved Fc gamma R- glycan discriminates between fucosylated and afucosylated IgG in humans and mice

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    The binding strength between IgG and Fc gamma R is influenced by the composition of the N-linked glycan at position N297 in the Fc-domain of IgG. Particularly, afucosylation increases the binding affinity of human IgG1 to human Fc gamma RIIIa up to similar to 20 fold, and additional galactosylation of the afucosylated IgG increases the affinity up to similar to 40 fold. The increase in affinity for afucosylated IgG has previously been shown to depend on direct carbohydrate carbohydrate interactions between the IgG-Fc glycan with an N-linked glycan at position 162 unique to hFc gamma RIIIa and hFc gamma RIIIb. Here we report that the N162 glycosylation site is also found in the orthologous mouse Fc gamma R, mFc gamma RIV. The N162-glycan in mFc gamma RIV was also responsible for enhancing the binding to mouse IgG with reduced fucose similar to hFc gamma RIIIa. However, unlike hFc gamma RIIIa, mFc gamma RIV did not bind more avidly to IgG with increased galactose and reduced fucose. Overall, these results suggest the N162-glycan in the human Fc gamma RIII family and its orthologous mouse Fc gamma RIV to be functionally conserve
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