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| 2. |
- Hellqvist, Eva, 1978-
(författare)
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Antigen interaction with B cells in two proliferative disorders : CLL and MGUS
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of the work presented in this thesis was to elucidate B cell interaction with antigen in the two B cell proliferative disorders chronic lymphocytic leukemia (CLL) and monoclonal gammopathy of undetermined significance (MGUS). In the first part we investigated the antigen specificity of CLL cells and characterized Epstein-Barr virus (EBV)-transformed CLL cell lines with regard to phenotype and genotype. The second part consists of studies on the antigen presenting capacity of myelin protein zero (P0) specific MGUS B cells and their relation to T cells and development of polyneuropathy.The aim of the work presented in this thesis was to elucidate B cell interaction with antigen in the two B cell proliferative disorders chronic lymphocytic leukemia (CLL) and monoclonal gammopathy of undetermined significance (MGUS). In the first part we investigated the antigen specificity of CLL cells and characterized Epstein-Barr virus (EBV)-transformed CLL cell lines with regard to phenotype and genotype. The second part consists of studies on the antigen presenting capacity of myelin protein zero (P0) specific MGUS B cells and their relation to T cells and development of polyneuropathy.CLL cells are considered antigen experienced and different patient-derived CLL cells expressing B cell receptors (BCR) with highly homologous antigen binding sites are believed to have been selected by a common antigen at some point during the leukemogenesis. In paper I we investigated the antigen specificity of CLL-cell derived antibodies (Abs) with various IGHV gene usage and stereotyped BCR subset belonging. Identified CLL antigens included vimentin, filamin B, cofilin-1, proline rich acidic protein-1, cardiolipin, oxidized low density lipoprotein and Streptococcus pneumoniae capsular polysaccharides. Many of the CLL Abs studied displayed an oligo- or polyreactive antigen binding pattern and the identified antigens were either associated with apoptotic cells or microbial infection. This is similar to what has been described for innate natural antibodies, possibly indicating that CLL cells are derived from a natural-antibody- producing B cell population. Further characterization of CLL homology subset-2 antigen specificity showed binding to glands in human gastric mucosa corpus tissue sections for a CLL homology subset-2 Ab with HCDR3 motif-1, suggesting that this CLL subset recognize an autoantigen much like the CLL Abs tested in Paper I.Characterization of EBV-transformed CLL and normal lymphoblastoid cell lines (LCLs) in paper II showed that eight of the CLL cell lines were verified to be of authentic neoplastic origin. Indication for a biclonal CLL was found in two of the cell lines and two of the presumably normal LCLs turned out to represent the malignant CLL clone. For three cell lines no conclusive evidence for CLL origin could be found emphasizing the importance of verifying the identity of cell lines used in research.
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| 3. |
- Hellqvist, Eva, 1978-, et al.
(författare)
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Myelin protein zero is naturally processed in IgM MGUS B cells : Aberrant triggering of patient T cells
- 2010
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 95:4, s. 627-636
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Monoclonal gammopathy of undetermined significance (MGUS) of IgM isotype is a condition with clonally expanded B cells, recently suggested having an infectious origin. MGUS is frequently associated with polyneuropathy and antibodies against myelin protein zero (P0), whereas the role of the T cells remains largely unknown. Here we have analyzed P0-specific B cells, as antigen-presenting cells, and their capacity to activate T helper cells. Design and Methods: We used a well-characterized MGUS-derived B cell line, TJ2, expressing anti-P0 IgM. The ability of TJ2 cells to bind, endocytose, process, and present P0 was investigated by receptor-clustering and immunofluorescence. The activation of P0-specific autologous T cells was studied by measuring IL2 and IFNγ with flow cytometry, immunobeads, and ELISPOT. Results: Surface-receptor clustering and endocytosis of receptor-ligand (IgM/P0) complexes were pronounced after P0 exposure. Naturally processed or synthetic P0 peptide (194-208)-pulsed TJ2 cells significantly induced IL2 secretion from autologous T cells compared to control antigen pulsed cells (p<0 .001). The numbers of IFNγ producing T helper cells, including CD4+/CD8+ cells, were also significantly increased (p=0.0152). Affinity-isolated naturally processed myelin peptides were potent IFNγ stimulators for autologous PBMCs, but not for control PBMCs. Interpretation and conclusions: We show for the first time that myelin P0 is naturally processed in IgM MGUS B cells, acting as aberrant antigen-presenting cells in activation of patients T helper cells. Our findings cast new light on the important role of autoreactive P0-specific B cells in he induction of the pathogenic T cell responses found in nerve lesions of MGUS patients with peripheral neuropathy.
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| 4. |
- Hellqvist, Lena, 1960-, et al.
(författare)
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Effect of nicotine-free and nicotine-containing snus on plaque pH in vivo
- 2012
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Ingår i: Swedish Dental Journal. - : Swedish Dental Journal. - 0347-9994. ; 36:4, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Syftet med studien var att utvärdera pH-förändringar i plack in vivo vid användning av olika nikotinfritt och nikotinhaltigt snus. Kolhydratinnehållet i produkterna analyserades också. Tio deltagare, alla snusanvändare, deltog i en experimentell tvärsnittsstudie, vid elva tillfällen, med en veckas mellanrum. Sex nikotinfria och fyra nikotininnehållande produkter på den svenska marknaden ingick i studien och en sackaroslösning användes som kontroll. Deltagarna borstade inte tänderna under tre dagar innan besöket och avstod från att äta, dricka och snusa/röka två timmar före varje test. pH mättes i tre approximalrum upp till 45 minuter med snusprodukten placerad under överläppen. De nikotininnehållande produkterna innehöll endast spår av glukos, fruktos och sackaros (0.5-1%) och stärkelse (1.5%), medan de nikotinfria produkterna innehöll upp till 6.5 % lågmolekylära kolhydrater och 26.0 % stärkelse. Resultatet av pH-mätningarna i plack visade att alla fyra nikotininnehållande produkter höjde pH, till skillnad från tre av de sex nikotinfria produkterna, som sänkte pH betydligt. Dessa pH-förändringar i plack kan ha såväl positiv som negativ effekt på kariesrisken beroende på vilken produkt som används
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| 5. |
- Hellqvist, Lena, et al.
(författare)
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Effect of nicotine-free and nicotine-containing snus on plaque pH in vivo
- 2012
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Ingår i: Swedish Dental Journal. - 0347-9994. ; 36:4, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate pH changes in plaque in vivo during the use of nicotine- free and nicotine-containing snus. The carbohydrate content of the products was also analysed. Ten subjects, all regular snus users, participated in an experimental cross-over study, on eleven occasions with an interval of one week. Six nicotine-free and four nicotine-containing products, which are sold on the Swedish market, were included and a sucrose solution was used as a control. The subjects did not brush their teeth for three days before coming to the laboratory, without eating, drinking or using snus/smoking for two hours prior to the test. pH was measured at three approximal sites up to 45 min with the test product placed under the upper lip. The carbohydrate analysis showed that the nicotine-containing products contained only traces of glucose, fructose and sucrose (0.5-1%) and starch (1.5%). Some of the nicotine-free products contained up to 6.5% low-molecular-weight carbohydrates and 26.0% starch. The intraoral pH measurements showed that four nicotine-containing products increased the plaque pH, in contrast to three of the six nicotine-free products, which lowered the pH. These pH changes may have an effect on the caries risk, both positively and negatively, depending on which product is used.
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| 6. |
- Hugoson, Anders, et al.
(författare)
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Dental caries in relation to smoking and the use of Swedish snus: epidemiological studies covering 20 years (1983-2003)
- 2012
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Ingår i: Acta Odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 70:4, s. 289-296
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of this study was to evaluate some intra-oral caries-associated variables and tobacco use on dental caries. Materials and methods. The participants were randomly recruited from three cross-sectional studies in Jonkoping, Sweden, in 1983, 1993 and 2003. Each study consisted of 130 individuals in each of the 20, 30, 40, 50, 60 and 70-year age groups. Of these, 550, 552 and 523 dentate individuals attended respective year of examination. They were all examined both clinically and radiographically. A questionnaire was completed in conjunction with the examination. In the studies, 345 were smokers, 104 snus users and 1142 non-tobacco users, in total 1591 individuals. Results. In 1983 and 1993, there were no significant differences in mean DFS between non-users and smokers, but a statistically significantly higher mean DFS in comparison with snus users. In 2003, there was no statistically significant difference in mean DFS between the groups. Multiple regressions showed that, after adjusting for age, gender and socio-demographic variables, there was a statistically significant association between DFS and smoking in 1983 (smoking excluded in favour of lactobacilli when further analysed) and DFS and plaque index (PLI) in 1993. In 2003, there was no association, apart from buffer capacity (Power rising) between DFS and the examined intra-oral caries-associated variables and tobacco use. Conclusions. The results of these epidemiological studies, performed in 1993 and 2003, indicate that daily smoking or snus use does not increase the risk of dental caries.
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| 9. |
- Lindström, Anders, 1949-, et al.
(författare)
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Etablering, tillväxt och skador för plantor odlade i såddrör (Tubesprout™) - resultat efter två säsonger i fält
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Försöket visade på mycket god överlevnad för plantor odlade i såddrören, Tubesprout™. Efter två år var överlevnaden för dessa 91 % för tall och 79 % för gran. För miniplantorna odlade i Jiffy varierade överlevnaden efter två år mellan 84 (tall) och 64 % (gran). Lägst överlevnad efter både det första och andra året hade de större referensplantorna. Av dessa levde 67 % av tallplantorna och endast 45 % av granplantorna. Bidragande till den goda överlevelsen hos Tubesprout™-odlade plantor var få snytbaggeskador och nästan inga skador av torka. Det andra miniplantsystemet, Jiffy 18, klarade snytbaggen nästan lika bra som Tubesprout™, men drabbades istället av stora avgångar beroende på torka. Hylsan tycks förhindra uttorkning av plantan som annars är ett stort problem vid plantering på torra marker av små plantor. För de äldre täckrotsodlade referensplantorna var den mesta plantdöden orsakad av kraftiga snytbaggeskador. Granen var värst drabbad med drygt 50 % snytbaggedödade plantor efter två år, medan den plantavgång hos tall som var orsakad av snytbagge var 26 %. Några plantor som stod i Tubesprout™ på försöksytan blev dock uppryckta, sannolikt av kråkfåglar.
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| 10. |
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| 11. |
- Myhrinder, Anna Lanemo, 1975-, et al.
(författare)
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Molecular characterization of neoplastic and normal "sister" lymphoblastoid B-cell lines from chronic lymphocytic leukemia
- 2013
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 54:8, s. 1769-1779
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) B-cells resemble self-renewing CD5 + B-cells carrying auto/xeno-antigen-reactive B-cell receptors (BCRs) and multiple innate pattern-recognition receptors, such as Toll-like receptors and scavenger receptors. Integration of signals from BCRs with multiple surface membrane receptors determines whether the cells will be proliferating, anergic or apoptotic. To better understand the role of antigen in leukemogenesis, CLL cell lines producing monoclonal antibodies (mAbs) will facilitate structural analysis of antigens and supply DNA for genetic studies. We present here a comprehensive genotypic and phenotypic characterization of available CLL and normal B-cell-derived lymphoblastoid cell lines (LCLs) from the same individuals (n = 17). Authenticity and verification studies of CLL-patient origin were done by IGHV sequencing, fluorescence in situ hybridization (FISH) and DNA/short tandem repeat (STR) fingerprinting. Innate B-cell features, i.e. natural Ab production and CD5 receptors, were present in most CLL cell lines, but in none of the normal LCLs. This panel of immortalized CLL-derived cell lines is a valuable reference representing a renewable source of authentic Abs and DNA.
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| 12. |
- Rosén, Anders, et al.
(författare)
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Lymphoblastoid cell line with B1 cell characteristics established from a chronic lymphocytic leukemia clone by in vitro EBV infection
- 2012
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 1:1, s. 18-27
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) cells express the receptor for Epstein-Barr virus (EBV) and can be infected in vitro. Infected cells do not express the growth-promoting set of EBV-encoded genes and therefore they do not yield LCLs, in most experiments. With exceptional clones, lines were obtained however. We describe a new line, HG3, established by in vitro EBV-infection from an IGHV1-2 unmutated CLL patient clone. All cells expressed EBNA-2 and LMP-1, the EBV-encoded genes pivotal for transformation. The karyotype, FISH cytogenetics and SNP-array profile of the line and the patient's ex vivo clone showed biallelic 13q14 deletions with genomic loss of DLEU7, miR15a/miR16-1, the two micro-RNAs that are deleted in 50% of CLL cases. Further features of CLL cells were: expression of CD5/CD20/CD27/CD43 and release of IgM natural antibodies reacting with oxLDL-like epitopes on apoptotic cells (cf. stereotyped subset-1). Comparison with two LCLs established from normal B cells showed 32 genes expressed at higher levels (> 2-fold). Among these were LHX2 and LILRA. These genes may play a role in the development of the disease. LHX2 expression was shown in self-renewing multipotent hematopoietic stem cells, and LILRA4 codes for a receptor for bone marrow stromal cell antigen-2 that contributes to B cell development. Twenty-four genes were expressed at lower levels, among these PARD3 that is essential for asymmetric cell division. These genes may contribute to establish precursors of CLL clones by regulation of cellular phenotype in the hematopoietic compartment. Expression of CD5/CD20/CD27/CD43 and spontaneous production of natural antibodies may identify the CLL cell as a self-renewing B1 lymphocyte.
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