Extension of the Color Glass Condensate Approach to Diffractive Reactions

We present an evolution equation for the Bjorken x dependence of diffractive dissociation on hadrons and nuclei at high energies. We extend the formulation of Kovchegov and Levin by relaxing the factorization assumption used there. The formulation is based on a technique used by Weigert to describe interjet energy flow. The method can be naturally extended to other exclusive observables

Optimal Detection of Rotations about Unknown Axes by Coherent and Anticoherent States

Coherent and anticoherent states of spin systems up to spin j=2 are known to be optimal in order to detect rotations by a known angle but unknown rotation axis. These optimal quantum rotosensors are characterized by minimal fidelity, given by the overlap of a state before and after a rotation, averaged over all directions in space. We calculate a closed-form expression for the average fidelity in terms of anticoherent measures, valid for arbitrary values of the quantum number j. We identify optimal rotosensors (i) for arbitrary rotation angles in the case of spin quantum numbers up to j=7/2 and (ii) for small rotation angles in the case of spin quantum numbers up to j=5. The closed-form expression we derive allows us to explain the central role of anticoherence measures in the problem of optimal detection of rotation angles for arbitrary values of j.Comment: 18 pages, 6 figures, 1 tabl

Autoreactive B Cells in the Marginal Zone that Express Dual Receptors

Allotype and isotype exclusion is a property of most lymphocytes. The reason for this property is not known but it guarantees a high concentration of a single receptor, and threshold numbers of receptors may be required for efficient positive and negative selection. Receptor editing compromises exclusion by sustaining recombination even after a functional receptor is formed. Consequently, B cells expressing multiple receptors arise. We have studied such B cells in which one of the two receptors is anti-self, and find that these partially autoreactive B cells accumulate in the marginal zone. The restriction of these cells in this location may help to prevent them from undergoing diversification and developing into fully autoreactive B cells

Die Bedeutung von SUMOyliertem HSP90 bei hämatologischen Neoplasien und soliden Tumoren

Nach hyperphosphoryliertem Paratarg-7 konnte die Arbeitsgruppe um Prof. Dr. med. M. Pfreundschuh mit SUMOyliertem HSP90 (HSP90-SUMO) ein zweites dominantes antigenes Target von Paraproteinen identifizieren, welches einen molekularen Risikofaktor für die Entwicklung einer Monoklonalen Gammopathie unbestimmter Signifikanz (MGUS), eines Multiplen Myeloms (MM) und eines Morbus Waldenstroem (WM) darstellt. Basierend auf der Annahme, dass posttranslationale Modifikationen eine entscheidende Rolle im autoimmunen Charakter von Epitopen spielen können, wurden Protein-Macroarrays in vitro SUMOyliert und anschließend auf Reaktivität mit Seren von Patienten mit einer Plasmazelldyskrasie (PCD) getestet. So kam es zur Entdeckung des SUMOylierten Hitzeschockprotein 90 als paraproteinärer Zielstruktur. Bei einer Verdünnung der Patientenseren von 1:10⁷ reagierten 11,9% der europäischen Patienten, 11,2% der afroamerikanischen Patienten und 5,1% der japanischen Patienten mit HSP90-SUMO. In keinen von über 900 Seren gesunder Kontrollen konnten Antikörper gegen HSP90-SUMO gefunden werden. Die Prävalenz von HSP90-SUMO-Trägern in der gesunden Population lag bei maximal 2%, woraus sich folgern lässt, dass die Trägerschaft von HSP90-SUMO mit einer deutlichen Risikoerhöhung für die Entwicklung einer Plasmazelldyskrasie einhergeht. Die Odds Ratio variierte je nach ethnischer Zugehörigkeit und lag bei maximal 14,8 in der Gruppe der Europäer. HSP90-SUMO wird autosomal dominant vererbt und ist zurückzuführen auf eine substratspezifische Inaktivierung der Sentrin-spezifische Protease 2 (SENP2). Im Rahmen dieser Arbeit wurden Patienten mit ausgewählten hämatologischen Neoplasien und soliden Tumoren mittels ELISA auf das Vorhandensein von SUMOyliertem HSP90 untersucht. Es konnte keine gehäufte Prävalenz bei diesen Erkrankungen nachgewiesen werden. Dies bestätigt, dass HSP90-SUMO ein spezifisches Phänomen bei Plasmazelldyskrasien ist, pathogenetisch im Rahmen einer chronischen Antigenstimulation von Bedeutung sein könnte und nicht generell mit neoplastischen Veränderungen vergesellschaftet ist.After Paratarg-7 SUMOylated HSP90 (HSP90-SUMO) is another dominant antigenic target of paraproteins in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS) and Waldenstroem's macroglobulinemia (WM), identified and characterized by the research team among Prof. M. Pfreundschuh. Based on the perception that posttranslational modification of proteins might increase the autoimmune character of epitopes, protein-macroarrays were SUMOylated in vitro and tested for reactivity with sera of patients suffering from a plasma cell dyscrasia (PCD). This led to the identification of HSP90-SUMO as a target of paraproteins. At a dilution of 1:10⁷ sera from 11.9% of European patients, 11.2% of Afro-American patients and 5.1% of Japanese patients reacted with HSP90-SUMO whereas no anti-HSP90-SUMO antibodies were detected in the sera of over 900 healthy controls. The prevalence of HSP90-SUMO carriers in healthy controls was 2% demonstrating that the carrier state is a risk factor for developing a plasma cell dyscrasia with a maximum odds ratio of 14,8 in the European population. HSP90- SUMO is inherited in an autosomal dominant fashion and due to a substrate-specific inactivation of sentrin-specific protease 2 (SENP2). The aim of this study was to examine the prevalence of HSP90-SUMO in patients with selected haematological neoplasm and solid tumours by ELISA. The frequency of HSP90-SUMO in these patients was shown to be similar to the one in healthy controls. This led to the conclusion that HSP90-SUMO is specific for MM, MGUS and WM, and that it might play a role in the pathogenesis of these diseases, for example by chronic antigenic stimulation. HSP90-SUMO carrierstate is not associated to neoplastic disorders in general

Editing Anti-DNA B Cells by Vλx

Receptor editing is performed by replacement of Vκ genes that contribute to autoreactivity. In addition, the Cκ locus can be deleted by Vκ rearrangement to intronic or 3′ of Cκ RS sequences (also referred to as κ deletion elements). B cells that delete the Cκ can then express λ light chains. However, the λ locus, either of man or mouse, does not allow V gene replacement. Nor does it appear to be deleted. Therefore, editing of autoreactive λ B cells may require alternative pathways. We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of λ1 in association with an anti-DNA heavy chain often coexpress a κ chain that prevents DNA binding. We speculate that such isotypically included cells may have low anti-DNA receptor densities, a feature that may lead to self-tolerance. Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the Vλ family, Vλx. The λx B cells of the tgs also express CD25 and may represent B cells that have exhausted light chain editing possibilities

Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern

We have studied the regulation of anti–DNA B cells in transgenic mice with a heavy chain transgene (3H9H/56R). This transgene codes for a heavy chain that forms anti–double-stranded DNA (dsDNA) antibody when paired with most members of the endogenous Vκ repertoire, but certain L chains, referred to as Vκ editors, do not sustain dsDNA binding in combination with 3H9H/56R. In the nonautoimmune 3H9H/56R BALB/c, most B cells generated do not bind DNA because the transgene itself is edited or is associated with a Vκ editor. A minor population of B cells (30%) bind dsDNA and express the λ1 light chain (known to sustain 3H9H/56R DNA binding). These 3H9/56R/λ1 B cells coexpress a κ editor, and we propose that the down-regulation of the anti-DNA BCR caused by the dual L chain expression may prevent activation of this κ/λ population. These κ/λ B cells are sequestered in the marginal zone. Here, we studied the influence of autoimmunity on expression and regulation of 3H9H/56R. In 3H9H/56R MRL/lpr mice, the expression of anti-dsDNA is vastly accelerated. Anti–dsDNA B cells use noneditor κs but, in addition, most anti–dsDNA B cells have edited the heavy chain transgene. λ1 B cells (without the coexpression of a κ editor) are found and the κ/λ1 MZ population is absent. Our results suggest that improper editing and failure to sequester autoreactive B cells may contribute to the breakdown of tolerance in MRL/lpr mice

Secondary Heavy Chain Rearrangement: A Mechanism for Generating Anti–double-stranded DNA B Cells

The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This resulted in clonal expansion and selection of specific mutations in the anti–double-stranded (ds) DNA B cell population. These data, together with a high frequency of anti-dsDNA B cell clones recovered as hybridomas, suggested that anti-dsDNAs are the product of an antigen-driven immune response. Genetic analysis associated this response with the generation of anti-dsDNA B cells through secondary rearrangements that replaced the site-directed transgene (sd-tg) with endogenous VH genes