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Böhme, Jan
Publications (9 of 9) Show all publications
Rietz, C., Screpanti, V., Brenden, N., Böhme, J. & Fernandez, C. (2003). Overexpression of Bcl-2 in T cells affects insulitis in the nonobese diabetic mouse. Scandinavian Journal of Immunology, 57(4), 342-349
Open this publication in new window or tab >>Overexpression of Bcl-2 in T cells affects insulitis in the nonobese diabetic mouse
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2003 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 57, no 4, p. 342-349Article in journal (Refereed) Published
Abstract [en]

The nonobese diabetic (NOD) mouse is a useful model for human autoimmune diabetes. The gene for the anti-apoptotic protein Bcl-2 has previously been suggested as a probable susceptibility candidate for the NOD mouse disease. In this study, we investigated how overexpression of Bcl-2 in lymphocytes might affect insulitis in NOD mice. A bcl-2 transgene expressed constitutively under the SV40-promoter and the 5'Igh enhancer, Emu, was bred onto NOD background. Two bcl-2 transgenic NOD strains were produced and analysed, one with overexpression of Bcl-2 on only B cells and the other with overexpression of Bcl-2 on both B and T cells. Subsequent to verification of expression pattern and functionality of the transgene, insulitis intensity was investigated in different backcross generations of the two transgenic strains. Overexpression of Bcl-2 on both B and T cells leads to a statistically significant protection of the mice from insulitis compared with normal littermates. Overexpression of Bcl-2 on only B cells, on the other hand, does not have any statistically significant effect on insulitis. Possible mechanisms for the effect of Bcl-2 on insulitis in NOD mice are discussed.

National Category
Immunology
Identifiers
urn:nbn:se:sh:diva-15548 (URN)10.1046/j.1365-3083.2003.01244.x (DOI)000181862300006 ()12662297 (PubMedID)2-s2.0-0037384047 (Scopus ID)
Available from: 2012-02-21 Created: 2012-02-21 Last updated: 2017-12-07Bibliographically approved
Brenden, N. & Böhme, J. (1999). Differential MHC expression requirements for positive selection of separate TCR Vb families. Immunogenetics, 49(1), 1-6
Open this publication in new window or tab >>Differential MHC expression requirements for positive selection of separate TCR Vb families
1999 (English)In: Immunogenetics, ISSN 0093-7711, E-ISSN 1432-1211, Vol. 49, no 1, p. 1-6Article in journal (Refereed) Published
Abstract [en]

Positive selection has been proposed to be involved in protection from diabetes. We examined positive selection by fluorescence-activated cell sorter analyses in thymocytes of protected and susceptible E-transgenic and non-transgenic NOD mice. Three Vb families showed positive selection in E-transgenic mice. Vb6+CD4+ and Vb10+CD4+ thymocytes were found at higher frequencies in both protected NOD-Ea and susceptible NOD-DY mice. The increased frequencies of Vb13+CD8+ thymocytes were found in protected NOD-Ea mice only, and not in susceptible NOD-DY transgenic mice. These three Vb families were further examined in bone-marrow chimeras between NOD-Ea and non-transgenic NOD mice, where we could examine the contribution of E-expressing bone-marrow-derived cells in positive selection. We find that NOD-Ea→NOD-Ea chimeras have an increased positive selection of Vb13+CD8+ cells and that positive selection is more efficient when both thymic epithelium and bone-marrow-derived cells express the E molecule. This was also seen for Vb6+CD4+ cells. However, for Vb6, bone-marrow-derived cells alone were also capable of positive selection. Positive selection of Vb10+CD4+ cells was restricted to E-expressing thymic epithelium only. For Vb13+CD8+ cells, we found that positive selection is most efficient with E-expression on both thymic epithelium and bone-marrow-derived cells, although positive selection also occurs with E-positive epithelium only. For Vb6+CD4+ cells, the dominating selecting cells are bone-marrow-derived cells, and Vb10+CD4+ cells seem to be selected exclusively by the thymic epithelium. Thus, the conditions for positive selection seem to vary considerably between different Vb families.

Keywords
Bone marrow, Postive selection, Thymic epithelium, Vb-NOD, cd4 antigen, cd8 antigen, major histocompatibility antigen, t lymphocyte receptor, animal cell, animal experiment, antigen expression, article, bone marrow cell, cell selection, chimera, controlled study, diabetes mellitus, fluorescence activated cell sorter, genetic susceptibility, mouse, nonhuman, priority journal, thymocyte, transgenic mouse, Animals, Autoimmune Diseases, Bone Marrow Cells, Bone Marrow Transplantation, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Clonal Deletion, Diabetes Mellitus, Type 1, Female, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Histocompatibility Antigens Class II, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Transgenic, Radiation Chimera, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocyte Subsets, Thymus Gland, Animalia, Mus musculus
National Category
Immunology
Identifiers
urn:nbn:se:sh:diva-22927 (URN)10.1007/s002510050457 (DOI)000077297800001 ()9811963 (PubMedID)2-s2.0-0032953289 (Scopus ID)
Available from: 2014-04-07 Created: 2014-03-28 Last updated: 2017-12-05Bibliographically approved
Högstrand, K. & Böhme, J. (1999). DNA damage caused by etoposide and γ-irradiation induces gene conversion of the MHC in a mouse non-germline testis cell line. Mutation research, 423(1-2), 155-169
Open this publication in new window or tab >>DNA damage caused by etoposide and γ-irradiation induces gene conversion of the MHC in a mouse non-germline testis cell line
1999 (English)In: Mutation research, ISSN 0027-5107, E-ISSN 1873-135X, Vol. 423, no 1-2, p. 155-169Article in journal (Refereed) Published
Abstract [en]

We have explored the effects of γ-irradiation and etoposide on the gene conversion frequency between the endogenous major histocompatibility complex class II genes Abk and Ebd in a mouse testis cell line of non-germline origin with a polymerase chain reaction assay. Both γ-rays and etoposide were shown to increase the gene conversion frequency with up to 15-fold compared to untreated cells. Etoposide, which is an agent that stabilise a cleavable complex between DNA and DNA topoisomerase II, shows an increased induction of gene conversion events with increased dose of etoposide. Cells treated with γ-rays, which induce strand breaks, had an increased gene conversion frequency when they were subjected to low doses of irradiation, but increasing doses of irradiation did not lead to an increase of gene conversion events, which might reflect differences in the repair process depending on the extent and nature of the DNA damage. These results where DNA damage was shown to be able to induce gene conversion of endogenous genes in mouse testis cells suggests that the DNA repair system could be involved in the molecular genetic mechanism that results in gene conversion in higher eukaryotes like mammals.

Keywords
γ-Irradiation, DNA damage, Etoposide, Gene conversion, MHC, Mouse, carcinogen, DNA topoisomerase (ATP hydrolysing), major histocompatibility antigen class 2, animal cell, article, controlled study, DNA repair, eukaryote, gamma irradiation, germ cell, immunogenetics, male, mammal, nonhuman, polymerase chain reaction, priority journal, testis cell, Amino Acid Sequence, Animals, Base Sequence, Cells, Cultured, Crosses, Genetic, DNA Mutational Analysis, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Gamma Rays, Genes, MHC Class II, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Molecular Sequence Data, Sequence Alignment, Testis, Animalia, Eukaryota, Mammalia
National Category
Cell Biology
Identifiers
urn:nbn:se:sh:diva-22928 (URN)10.1016/S0027-5107(98)00239-5 (DOI)10029693 (PubMedID)2-s2.0-0033601827 (Scopus ID)
Available from: 2014-04-11 Created: 2014-03-28 Last updated: 2017-12-05Bibliographically approved
Brenden, N., Rietz, C. & Böhme, J. (1999). E expression is needed on both bone marrow derived cells and thymic epithelium to increase IL-4 production and achieve protection in NOD bone marrow chimeras. Cytokine, 11(10), 766-772
Open this publication in new window or tab >>E expression is needed on both bone marrow derived cells and thymic epithelium to increase IL-4 production and achieve protection in NOD bone marrow chimeras
1999 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 11, no 10, p. 766-772Article in journal (Refereed) Published
Abstract [en]

The NOD mouse is an animal model for insulin-dependent diabetes with many similarities to the human disease. NOD mice which are transgenic for the Ea gene, allowing expression of the E molecule, are protected from diabetes and rarely develop insulitis. We have constructed bone marrow chimeras between transgenic and non-transgenic NOD mice to study the correlation of E expression on bone marrow derived cells and thymic epithelium vs the production of IL-4 and IFN-γ. We show that NOD-E→NOD-E and NOD-E→NOD chimeras have elevated levels of IL-4 compared to NOD→NOD and NOD→NOD-E chimeras in the thymus. However, in the periphery the protected NOD-E→NOD-E show much higher IL-4 levels than any of the other chimeras. This drop in peripheral IL-4 production seen in NOD-E→NOD, NOD→NOD-E and NOD→NOD chimeras correlates with the increased insulitis seen in these mice compared to NOD-E→NOD-E. In contrast, there were no differences in IFN-γ production between the chimeras. We suggest that the precommitted, regulatory T cells, selected in an E-expressing thymic environment, need continuous interaction with E-expressing primary antigen presenting cells in the periphery for optimal IL-4 production. Decrease in IL-4 production correlates with increased insulitis.

Keywords
Bone marrow chimeras, Diabetes, IL-4, NOD-E, cytokine, gamma interferon, interleukin 4, animal cell, animal experiment, animal model, animal tissue, antigen presenting cell, article, bone marrow cell, chimera, controlled study, cytokine production, female, gene expression, insulin dependent diabetes mellitus, insulitis, mouse, nonhuman, priority journal, t lymphocyte, thymocyte, transgene, Animals, B-Lymphocytes, Bone Marrow Cells, Bone Marrow Transplantation, Diabetes Mellitus, Type 1, Epithelial Cells, Histocompatibility Antigens Class II, Inflammation, Interferon Type II, Interleukin-4, Islets of Langerhans, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Transgenic, Radiation Chimera, Spleen, Thymus Gland, Animalia
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-22922 (URN)10.1006/cyto.1998.0482 (DOI)000082855700006 ()10525315 (PubMedID)2-s2.0-0032823096 (Scopus ID)
Available from: 2014-04-07 Created: 2014-03-28 Last updated: 2017-12-05Bibliographically approved
Högstrand, K. & Böhme, J. (1999). Gene conversion of major histocompatibility complex genes is associated with CpG-rich regions. Immunogenetics, 49(5), 446-455
Open this publication in new window or tab >>Gene conversion of major histocompatibility complex genes is associated with CpG-rich regions
1999 (English)In: Immunogenetics, ISSN 0093-7711, E-ISSN 1432-1211, Vol. 49, no 5, p. 446-455Article in journal (Refereed) Published
Abstract [en]

We examined 32 DNA sequences of mouse and human major histocompatibility complex (MHC) genes believed to have been subjected to gene conversion events. All regions of the mouse H2 genes as well as the human HLA genes which have been implied to be involved in gene conversion events had elevated levels of CpG dinucleotides, whereas the rest of the genes showed extensive CpG suppression. Mouse MHC genes which have been suspected but not directly implied to be involved in gene conversion events also showed elevated levels of CpG dinucleotides. Moreover, both mouse and human MHC genes which have never been suspected of undergoing gene conversion had low levels of CpG throughout the genes. These results indicate that high CpG levels are correlated with gene conversion rather than with polymorphism, as non-polymorphic genes that have been implicated as gene conversion donors also have elevated levels of CpG dimers in the involved regions whereas polymorphic genes which have never been considered to undergo gene conversion events have a low level of CpG dinucleotides. We also studied the methylation pattern of CpG dimers in the Abk gene by restriction enzyme digestion of mouse testis DNA followed by Southern blot and hybridization to an Abk-specific probe. The examined CpG dimers in prepubescent mice, where the latest germline stages are spermatogonia, leptene, or pachytene, are respectively non-methylated. Accordingly, the CpG dimers appear to be non-methylated in germline DNA from the testis of prepubescent mice, where gene conversions have been reported to occur.

Keywords
CpG, Gene conversion, H2, HLA, MHC, Mouse, dinucleotide, restriction endonuclease, animal cell, article, controlled study, DNA methylation, DNA sequence, histocompatibility gene, major histocompatibility complex, nonhuman, pachytene, priority journal, southern blotting, spermatogonium, Animals, Chimera, Dimerization, Dinucleoside Phosphates, Genes, MHC Class II, Germ Cells, H-2 Antigens, Histocompatibility Antigens, HLA Antigens, Humans, Liver, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Sexual Maturation, Testis
National Category
Immunology
Identifiers
urn:nbn:se:sh:diva-22926 (URN)10.1007/s002510050518 (DOI)10199921 (PubMedID)2-s2.0-0032923098 (Scopus ID)
Available from: 2014-04-11 Created: 2014-03-28 Last updated: 2017-12-05Bibliographically approved
Rietz, C., Pilström, B., Brenden, N. & Böhme, J. (1999). Minute defects in the expression of MHC E molecules lead to impaired protection from autoimmunity in NOD mice. Scandinavian Journal of Immunology, 50(4), 405-410
Open this publication in new window or tab >>Minute defects in the expression of MHC E molecules lead to impaired protection from autoimmunity in NOD mice
1999 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 50, no 4, p. 405-410Article in journal (Refereed) Published
Abstract [en]

The E complex of the major histocompatibility complex (MHC) can prevent the spontaneous development of diabetes in nonobese diabetic (NOD) mice transgenic for the Ea gene. None of three promoter-mutated Ea constructs with Ea expression directed to different subsets of immunocompetent cells exerts full protection in NOD mice. The promoter-mutated constructs are all capable of mediating intrathymic elimination of I-E-restricted T cells. Thus, thymic negative selection is not responsible for the protective effect but a more complex effect is likely. Here we show that combinations of two or three different mutated Ea constructs do not protect against intra-islet insulitis either. We also show that spleen cells from protected animals are sufficient to protect NOD mice in adoptive transfer experiments. The only detectable expression defects in splenic cells or cells influencing the repertoire of splenic cells are in the B-cell compartment. Furthermore, in three construct combinations, the differences to wild-type expression are extremely small. Thus, we conclude that even minute disturbances of the E expression pattern might reduce the protection of NOD mice from insulitis.

Keywords
allele, animal cell, animal experiment, animal model, article, autoimmunity, b lymphocyte, gene expression, gene mutation, helper cell, immunocompetent cell, insulitis, lymphocytic infiltration, major histocompatibility complex, mouse, nonhuman, priority journal, promoter region, spleen cell, transgene, Adoptive Transfer, Animals, Cell Transplantation, Diabetes Mellitus, Type 1, Genes, MHC Class I, H-2 Antigens, Histocompatibility Antigens Class I, HLA Antigens, Islets of Langerhans, Mice, Mice, Inbred NOD, Mice, Mutant Strains, Mice, Transgenic, Pancreatitis, Spleen
National Category
Immunology
Identifiers
urn:nbn:se:sh:diva-22921 (URN)10.1046/j.1365-3083.1999.00613.x (DOI)000082891600010 ()10520181 (PubMedID)2-s2.0-0032885228 (Scopus ID)
Available from: 2014-05-05 Created: 2014-03-28 Last updated: 2017-12-05Bibliographically approved
Brenden, N. & Böhme, J. (1998). Disease-protected major histocompatibility complex Ea-transgenic non- obese diabetic (NOD) mice show interleukin-4 production not seen in susceptible Ea-transgenic and non-transgenic NOD mice. Immunology, 95(1), 1-7
Open this publication in new window or tab >>Disease-protected major histocompatibility complex Ea-transgenic non- obese diabetic (NOD) mice show interleukin-4 production not seen in susceptible Ea-transgenic and non-transgenic NOD mice
1998 (English)In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 95, no 1, p. 1-7Article in journal (Refereed) Published
Abstract [en]

The non-obese diabetic (NOD) mouse is an animal model for insulin- dependent diabetes that has many similarities to the human disease. NOD mice transgenic for the Ea gene, allowing expression of the E molecule, are protected from diabetes and rarely develop insulitis. An Ea transgene mutated in the promoter region, (ΔY) lacks E expression on most B cells, thymic medullary epithelium and primary antigen-presenting cells, and confers no protection whatsoever. We have used these transgenic NOD mice, together with non-transgenic NOD mice, to study the correlation of E expression and production of interleukin-4 (IL-4) and interferon-γ (IFN-γ). We show that protected E-transgenic NOD mice have elevated levels of IL-4 compared with non-transgenic mice, both in the thymus and in the periphery. However, susceptible ΔY-transgenic mice have elevated thymic IL-4 levels, but express almost as little IL-4 as non-transgenic NOD mice in the periphery. This drop in peripheral IL-4 production seen in ΔY-transgenic mice thus correlates with the decreased E expression in the periphery of ΔY-transgenic NOD mice. In contrast, there were no differences in IFN-γ production between the three NOD lines. We suggest that Ea-transgenic NOD mice have E-selected regulatory T cells producing IL-4, which are subsequently activated by E-expressing primary antigen-presenting cells in the periphery. This activation would then be instrumental for the E-mediated protection from disease in NOD mice. Such a process would explain the total absence of protection in ΔY-transgenic NOD mice, despite their widespread E expression.

Keywords
cd4 antigen, cd8 antigen, gamma interferon, interleukin 4, major histocompatibility antigen class 2, messenger rna, animal cell, animal experiment, animal model, animal tissue, article, controlled study, disease predisposition, gene mutation, insulin dependent diabetes mellitus, insulitis, major histocompatibility complex, mouse, nonhuman, priority journal, promoter region, protection, t lymphocyte, transgenic mouse, Animals, Cells, Cultured, Diabetes Mellitus, Type 1, Enzyme-Linked Immunosorbent Assay, Gene Expression, Genetic Predisposition to Disease, Histocompatibility Antigens Class I, HLA Antigens, Interferon Type II, Interleukin-4, Mice, Mice, Inbred NOD, Mice, Transgenic, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Spleen, T-Lymphocytes, Thymus Gland
National Category
Immunology
Identifiers
urn:nbn:se:sh:diva-22931 (URN)10.1046/j.1365-2567.1998.00580.x (DOI)000075792400001 ()9767450 (PubMedID)2-s2.0-0031661151 (Scopus ID)
Available from: 2014-04-07 Created: 2014-03-28 Last updated: 2017-07-20Bibliographically approved
Högstrand, K. & Böhme, J. (1997). Gene conversion of major histocompatibility complex genes in the mouse spermatogenesis is a premeiotic event. Molecular Biology of the Cell, 8(12), 2511-2517
Open this publication in new window or tab >>Gene conversion of major histocompatibility complex genes in the mouse spermatogenesis is a premeiotic event
1997 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 8, no 12, p. 2511-2517Article in journal (Refereed) Published
Abstract [en]

The molecular genetic mechanism of gene conversion in higher eukaryotes remains unknown. We find it of considerable interest to determine when during spermatogenesis gene conversion occurs. We have therefore purified pachytene spermatocytes and haploid spermatocytes from adult mice and analyzed these fractions for the presence of gene conversion products resulting from the transfer between the major histocompatibility complex class II genes Ebd and Abk in a polymerase chain reaction assay. We have further isolated spermatogenic cells from prepubescent mice and analyzed them for the presence of the same gene conversion products. We can detect gene conversion products in testis cells as early as in 8-d-old mice where the only existing spermatogenic cells are spermatogonia. The frequency of gene conversion products remains the same as the cells reach meiosis in 18-d-old mice, and is unchanged after meiosis is completed in haploid spermatocytes. Gene conversion of this specific fragment therefore appears to be a premeiotic event and, consequently, relies on genetic mechanisms other than normal meiotic recombination.

National Category
Cell Biology
Identifiers
urn:nbn:se:sh:diva-23003 (URN)A1997YK93000012 ()9398672 (PubMedID)2-s2.0-1842293381 (Scopus ID)
Available from: 2014-04-11 Created: 2014-04-11 Last updated: 2017-07-20Bibliographically approved
Forsberg, L., Dannewitz, J., Nilsson, J., Kjellström, K., Petersson, E., Böhme, J. & Grahn, M. A ‘good genes’ effect from MHC super-genotypes in brown trout mediated by male competition and not by ornaments.
Open this publication in new window or tab >>A ‘good genes’ effect from MHC super-genotypes in brown trout mediated by male competition and not by ornaments
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(English)Article in journal (Refereed) Submitted
National Category
Natural Sciences
Identifiers
urn:nbn:se:sh:diva-16102 (URN)
Note
Som manuskript i avhandling. As manuscript in dissertation.Available from: 2008-05-06 Created: 2012-04-23 Last updated: 2013-09-25Bibliographically approved
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