Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction

Somatic hypermutation specifically modifies rearranged immunoglobulin (Ig) genes in germinal center (GC) B cells. However, the bcl-6 gene can also acquire somatic mutations during the GC reaction, indicating that certain non-Ig genes can be targeted by the somatic hypermutation machinery. The CD95 gene, implicated in negative selection of B lymphocytes in GCs, is specifically expressed by GC B cells and was recently identified as a tumor suppressor gene being frequently mutated in (post) GC B cell lymphomas. In this study, the 5′ region (5′R) and/or the last exon coding for the death domain (DD) of the CD95 gene were investigated in naive, GC, and memory B cells from seven healthy donors. About 15% of GC and memory, but not naive, B cells carried mutations within the 5′R (mutation frequency 2.5 × 10−4 per basepair). Mutations within the DD were very rare but could be efficiently selected by inducing CD95-mediated apoptosis: in 22 apoptosis-resistant cells, 12 DD mutations were found. These results indicate that human B cells can acquire somatic mutations of the CD95 gene during the GC reaction, which potentially confers apoptosis resistance and may counteract negative selection through the CD95 pathway

Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma

Recent work identified Hodgkin and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease (cHD) as clonal progeny of mature B cells. Therefore, it is generally assumed that cHD homogenously represents a B cell lymphoma. In a subset of cHD, however, H/RS cells expressing T cell–associated proteins may be candidates for alternative lineage derivation. Single H/RS cells with cytotoxic T cell phenotype were micromanipulated from three cases of cHD and analyzed by single cell polymerase chain reaction for immunoglobulin heavy (IgH) and light chain (IgL) gene rearrangements, T cell receptor (TCR)-β gene rearrangements, and germline configuration of the IgH and TCR-β loci. H/RS cells from two cases of cHD harbored clonal, somatically mutated Ig gene rearrangements, whereas TCR-β loci were in germline configuration. In contrast, H/RS cells from an additional case harbored clonal TCR-β variable/diversity/joining (VDJ) and DJ gene rearrangements, whereas the IgH locus was in germline configuration on both alleles. Thus, in two cases of cHD with H/RS cells expressing cytotoxic T cell molecules, the tumor cells are derived from mature B cells that aberrantly express T cell markers. In a third case, however, H/RS cells were derived from a T cell, demonstrating that cHD can also occur as a T cell lymphoma

Vereinfachte Bewertung von Umweltbelastungen

Mensch und Umwelt sind vielfältigen Umweltbelastungen ausgesetzt. Mit integriertenMethoden können auch Auswirkungen betrachtet werden, die in klassischen Ökobilanzen bisher nicht berücksichtigt wurden

Klimaschutz und Versorgungssicherheit

KLIMASCHUTZ UND VERSORGUNGSSICHERHEIT Klimaschutz und Versorgungssicherheit / Klaus, Thomas (Rights reserved) ( -

A climate protection strategy for Germany--40% reduction of CO2 emissions by 2020 compared to 1990

This paper presents measures and instruments for Germany to achieve the goal of 40% CO2-emission reduction until 2020 by reducing energy-related emissions by 224 million tonne (Mt). The most important measures in this regard are cuts in electricity generation (savings of 40 Mt), fuel switching and increased energy conversion efficiency (30 Mt) and an augmented 26% share of renewable energies in the provision of electrical energy (44 Mt). Average cost of the measures are at 50 euro per tonne avoided CO2, which corresponds to an additional monthly expenditure per household of less than 25 euro.Climate policy Mitigation Energy supply