Immunogenetic analysis of human follicle centre lymphomas and diffuse large cell lymphomas
Immunogenetic analysis of human follicle centre lymphomas and diffuse large cell lymphomas
This study focuses on diffuse large cell lymphomas (DLCL) and follicle center lymphomas (FCL), two entities that encompass ca 70-80% of B-cell malignancies. The aim was to characterize the VH gene usage and mutation patterns at diagnosis and to detect changes in these patterns over time. No skewing of VH gene segment usage was detected. VH genes showed a significant burden of somatic mutations, consistent with a germinal center (GC) origin. Analysis of the mutation patterns suggests antigen selection had occurred with selective pressure to maintain the framework regions of the VH genes. Detailed analysis of a large number of templates from presentation biopsies revealed that commonly DLCL are still responsive to the somatic mutation mechanisms in the GC, resulting in introclonal sequence heterogeneity. Lymphoma progression however can lead to the selection of a subclone with subsequent loss of this heterogeneity.
FCL and DLCL appear to commonly express RNA transcripts for multiple Ig isotypes. The sequencing data indicate the derivation of these transcripts from different cell populations and immunocytochemistry suggests that at least some of these transcripts are translated into protein and represent istoype switch events.
VH and VL sequences also provide patient specific tumour-associated antigens, which can be used as a target for immune attack. A phase I/II study is currently being undertaken based on this concept. Vaccines consisting of DNA containing VH and VL genes are being used to activate immunity against the cancer in patients with FCL. In a second part of this thesis heavy and light chain variable genes from patients with FCL were identified in preparation for a DNA vaccine study in this patient group. A pilot study of expressing the complete IgM of one of these patients in the baculovirus system was performed, as a tool for measuring anti-adiotype responses in patients with FCL before and after vaccination.
University of Southampton
Ottensmeier, Christian Hermann Heinrich
15164ded-c41c-4584-8c48-1be40b4d8c83
1999
Ottensmeier, Christian Hermann Heinrich
15164ded-c41c-4584-8c48-1be40b4d8c83
Ottensmeier, Christian Hermann Heinrich
(1999)
Immunogenetic analysis of human follicle centre lymphomas and diffuse large cell lymphomas.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
This study focuses on diffuse large cell lymphomas (DLCL) and follicle center lymphomas (FCL), two entities that encompass ca 70-80% of B-cell malignancies. The aim was to characterize the VH gene usage and mutation patterns at diagnosis and to detect changes in these patterns over time. No skewing of VH gene segment usage was detected. VH genes showed a significant burden of somatic mutations, consistent with a germinal center (GC) origin. Analysis of the mutation patterns suggests antigen selection had occurred with selective pressure to maintain the framework regions of the VH genes. Detailed analysis of a large number of templates from presentation biopsies revealed that commonly DLCL are still responsive to the somatic mutation mechanisms in the GC, resulting in introclonal sequence heterogeneity. Lymphoma progression however can lead to the selection of a subclone with subsequent loss of this heterogeneity.
FCL and DLCL appear to commonly express RNA transcripts for multiple Ig isotypes. The sequencing data indicate the derivation of these transcripts from different cell populations and immunocytochemistry suggests that at least some of these transcripts are translated into protein and represent istoype switch events.
VH and VL sequences also provide patient specific tumour-associated antigens, which can be used as a target for immune attack. A phase I/II study is currently being undertaken based on this concept. Vaccines consisting of DNA containing VH and VL genes are being used to activate immunity against the cancer in patients with FCL. In a second part of this thesis heavy and light chain variable genes from patients with FCL were identified in preparation for a DNA vaccine study in this patient group. A pilot study of expressing the complete IgM of one of these patients in the baculovirus system was performed, as a tool for measuring anti-adiotype responses in patients with FCL before and after vaccination.
This record has no associated files available for download.
More information
Published date: 1999
Identifiers
Local EPrints ID: 463639
URI: http://eprints.soton.ac.uk/id/eprint/463639
PURE UUID: d201c622-e9a1-4110-9767-cdd31f0b83a1
Catalogue record
Date deposited: 04 Jul 2022 20:54
Last modified: 23 Jul 2022 02:15
Export record
Contributors
Author:
Christian Hermann Heinrich Ottensmeier
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics