TY - JOUR A1 - Tony, H. P. A1 - Lehrnbecher, T. A1 - Merz, H. A1 - Sebald, Werner A1 - Wilhelm, M. T1 - Regulation of IL-4 responsiveness in lymphoma B cells N2 - The responsiveness to IL-4 with and without costimulation with anti-IgM antibodies or phorbolester was studied in 35 cases of low grade non-Hodgkin Iymphoma by analyzing enhancement of CD23 and HLA dass li expression. The predominant phenotype responds directly to IL-4. Separate differentiation states can be distinguished according to coordinate or differential upregulation of CD23 and HLA dass II molecules by IL-4 alone, and differences in responsiveness to anti-IgM antibodies. A particular subgroup of B-lymphoma cells defines a separate stage of B-eeil differentiation. They fail to express high affinity binding sites for IL-4 and accordingly do not respond to IL-4- mediated signals. Cross-linking membrane lgM receptors or direct activation of protein kinase C via phorbolester induces IL-4 receptor expression and subsequent IL-4 reactivity. KW - Biochemie KW - B lymphocytes KW - CD23 KW - CLL KW - HLA class ll KW - IL-4 KW - IL-4-receptor KW - membrane immunoglobulin Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62520 ER - TY - THES A1 - Klauss, Esther T1 - Immunhistochemische Untersuchungen zu Differenzierungsstadien der B-Lymphozyten in EBV-assoziierten Lymphoproliferationen T1 - Immunohistochemical inquiry into differentiation states of B lymphocytes in EBV associated lymphoproliferations N2 - Die vorliegende Arbeit hatte zur Aufgabe, die EBV-infizierte Zelle bei infektiöser Mononukleose, Hodgkin Lymphom, Post-Transplantations-Lymphoproliferation(PTLD) und seniler Lymphoproliferation zu beschreiben. Da die Einordnung der senilen Lymphoproliferation als eigenständige Entität unbefriedigend ist, sollte der Bezug zu PTLD oder Hodgkin Lymphom untersucht werden.Sowohl bezüglich des Latenztyps des EBV, der Oberflächenantigen- und Transkriptionsfaktorenexpression als auch der fehlenden Immunglobulinsekretion entsprachen sich Hodgkin Lymphom und senile Lymphoproliferation. Zwischen seniler Lymphoproliferation und PTLD dagegen fanden sich diesbezüglich große Unterschiede. Daher sind die senilen Lymphoproliferationen im Ergebnis dieser Doktorarbeit als Hodgkin Lymphome des höheren Alters anzusehen. Als Nebenbeobachtung stellten sich die hier untersuchten Hodgkin Zellen als CD27 negativ dar, die im Unterschied stehen, zur CD27 und CD30 positiven Memoryzelle, welche als korrespondierende Normalzelle postuliert wurde. Der Vergleich EBV-negativer und EBV-positiver Hodgkin Lymphome erbrachte in dieser Hinsicht jedoch keine Unterschiede. Die CD27-Negativität der Hodgkin Zelle ist somit nicht als EBV-spezifisches Phänomen zu verstehen und bedarf weiterer Klärung. N2 - This work´s aime was to describe the EBV infected cell in infectious monunnocleosis, hodgkin`s disease, post-transplatation lymphoproliferations (PTLD) and senile lymphoproliferation. The classification of senile lymphoproliferations as a independent entity is not satisfying. Therefore immunhistochemical stainigs were made to examin the relation between senile lymphoproliferations and PTLD and Hodgkin`s disease, respectively. As well as concerning the latency type of EBV, the expression of surface antigens and transcriptionfactors and the missing immunoglobulin synthesis Hodgkin`s disease and senile lymphoproliferation were equivalent to each other. Whereas in this respect significant differences between senile lymphoproliferation and PLTD were found. Thus the senile lymphoproliferations, as a result of this theses, can be considered as Hodgkin`s lymphomas in the elderly. As a side observeration the examined Hodgkin`s cells presented themselfs as CD27 negative. This is a unexpected difference to the CD27 and CD30 positive memory cell which was postulated as the corresponding regular cell. In this respect, the comparison between EBV positive ans EBV negative Hodgkin`s Lymphomas showed no distinct result. Therefore the CD27 negativity of the Hodgkin`s cell is not an EBV specific phenomenon and requires further investigation. KW - B-Lymphozyten KW - CD27 KW - EBV KW - Senile Lymphoproliferation KW - Extrafollikuläre Aktivierung KW - B lymphocytes KW - CD27 KW - EBV KW - senile lymphoproliferation KW - extrafollicular activation Y1 - 2007 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-22899 ER - TY - THES A1 - Kränzle, Heidi T1 - Analyse des Immunglobulinrepertoires in peripheren B-Zellen von Patienten mit systemischem Lupus Erythematodes T1 - The Analysis of the immunglobulin repertoire of peripheral B cells in systemic lupus erythematosus N2 - Mit Hilfe der Einzelzell PCR wurden CD 19+ B-Zellen aus dem peripheren Blut von zwei Patienten mit systemischen Lupus erythematodes isoliert und anschließend die Kappa-Leichtketten Rearrangements analysiert. Es konnten 194 nichtproduktiv und 221 produktiv rearrangierte Immunblobuline sequenziert werden und mit alterstypischen Repertoires verglichen werden. Dazu zählten die B-Zellen aus dem Nabelschnurblut, verschiedene B-Zellen der kindlichen Tonsille und B-Zellen aus dem Erwachsenenblut. Die Schwerpunkt der Analyse lagen dabei auf dem Aufbau des Kappa-Repertoire aus den einzelnen V-Kappa-Familien, auf der Modifikation der VkJk-Schnittstelle durch die verschiedenen Rekombiantionsenzyme (TdT, Exonukleasen, durch P- und N-Nukleotide sowie auf der Modifikation der Immunglobuline durch somatische Hypermutation. N2 - The human kappa chain repertoire form genomic VkJk rearrangements of individual peripheral CD19+ B cells of two patients with systemic lupus erythematosus were analysed by single cell PCR technique. 221 productive and 194 nonproduktive VkJk rearrangements were sequenced and compared to human cord blood VkJk repertoire, to different B cells from child tonsil and to adult peripheral B cell VkJk repertoire. The analysis includes the distribution of individual V-genes, the sequence diversity in the CDR3 provided by exonuclease activity, TdT-activitiy, p-nucleotide formation and the influence by somatic hypermutation. KW - Systemischer Erythematodes KW - Immunglobuline KW - Kappa Immunglobulinrepertoire KW - B Lymphozyten KW - kappa immunglobulinrepertoire KW - B lymphocytes Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-27369 ER - TY - JOUR A1 - Rodrigues, Lénia A1 - Popov, Nikita A1 - Kaye, Kenneth M. A1 - Simas, J. Pedro T1 - Stabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for \(\gamma\)-Herpesvirus Lymphoproliferation JF - PLoS PATHOGENS N2 - Host colonization by lymphotropic \(\gamma\)-herpesviruses depends critically on expansion of viral genomes in germinal center (GC) B-cells. Myc is essential for the formation and maintenance of GCs. Yet, the role of Myc in the pathogenesis of \(\gamma\)-cherpesviruses is still largely unknown. In this study, Myc was shown to be essential for the lymphotropic \(\gamma\)-herpesvirus MuHV- 4 biology as infected cells exhibited increased expression of Myc signature genes and the virus was unable to expand in Myc defficient GC B- cells. We describe a novel strategy of a viral protein activating Myc through increased protein stability resulting in increased progression through the cell cycle. This is acomplished by modulating a physiological posttranslational regulatory pathway of Myc. The molecular mechanism involves Myc heterotypic poly- ubiquitination mediated via the viral E3 ubiquitin- ligase mLANA protein. \(EC_5S^{mLANA}\) modulates cellular control of Myc turnover by antagonizing \(SCF^{Fbw7}\) mediated proteasomal degradation of Myc, mimicking \(SCF^{\beta-TrCP}\). The findings here reported reveal that modulation of Myc is essential for \(\gamma\)-herpesvirus persistent infection, establishing a link between virus induced lymphoproliferation and disease. KW - latency KW - murine gammaherpesvirus 68 KW - Epstein-Barr-virus KW - C-MYC KW - nuclear antigen KW - germinal center KW - B lymphocytes KW - protein KW - cells KW - beta-TRCP Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131227 VL - 9 IS - 8 ER -