Lymphoma-associated mutations in autoreactive memory B cells of patients with Sjögren's syndrome

We recently demonstrated that normal memory B lymphocytes carry a substantial number of de novo mutations in the genome. Here, we performed exome-wide somatic mutation analyses of bona fide autoreactive rheumatoid factor (RF)-expressing memory B cells retrieved from patients with Sjӧgren's syndrome (SS). The amount and repertoire of the de novo exome mutations of RF B cells were found to be essentially different from those detected in healthy donor memory B cells. In contrast to the mutation spectra of normal B cells, which appeared random and non-selected, the mutations of the RF B cells were greater in number and enriched for mutations in genes also found mutated in B-cell non-Hodgkin lymphomas. During the study, one of the SS patients developed a diffuse large B-cell lymphoma (DLBCL) out of an RF clone that was identified 2 years earlier in an inflamed salivary gland biopsy. The successive oncogenic events in the RF precursor clone and the DLBCL were assessed. In conclusion, our findings of enhanced and selected genomic damage in growth-regulating genes in RF memory B cells of SS patients together with the documented transformation of an RF-precursor clone into DLBCL provide unique novel insight into the earliest stages of B-cell derailment and lymphomagenesis.</p

Lymphoma-associated mutations in autoreactive memory B cells of patients with Sjögren's syndrome

We recently demonstrated that normal memory B lymphocytes carry a substantial number of de novo mutations in the genome. Here, we performed exome-wide somatic mutation analyses of bona fide autoreactive rheumatoid factor (RF)-expressing memory B cells retrieved from patients with Sjӧgren's syndrome (SS). The amount and repertoire of the de novo exome mutations of RF B cells were found to be essentially different from those detected in healthy donor memory B cells. In contrast to the mutation spectra of normal B cells, which appeared random and non-selected, the mutations of the RF B cells were greater in number and enriched for mutations in genes also found mutated in B-cell non-Hodgkin lymphomas. During the study, one of the SS patients developed a diffuse large B-cell lymphoma (DLBCL) out of an RF clone that was identified 2 years earlier in an inflamed salivary gland biopsy. The successive oncogenic events in the RF precursor clone and the DLBCL were assessed. In conclusion, our findings of enhanced and selected genomic damage in growth-regulating genes in RF memory B cells of SS patients together with the documented transformation of an RF-precursor clone into DLBCL provide unique novel insight into the earliest stages of B-cell derailment and lymphomagenesis.</p

25 Years of Self-Organized Criticality: Solar and Astrophysics

Shortly after the seminal paper “Self-Organized Criticality: An explanation of 1/fnoise” by Bak et al. (1987), the idea has been applied to solar physics, in “Avalanches and the Distribution of Solar Flares” by Lu and Hamilton (1991). In the following years, an inspiring cross-fertilization from complexity theory to solar and astrophysics took place, where the SOC concept was initially applied to solar flares, stellar flares, and magnetospheric substorms, and later extended to the radiation belt, the heliosphere, lunar craters, the asteroid belt, the Saturn ring, pulsar glitches, soft X-ray repeaters, blazars, black-hole objects, cosmic rays, and boson clouds. The application of SOC concepts has been performed by numerical cellular automaton simulations, by analytical calculations of statistical (powerlaw-like) distributions based on physical scaling laws, and by observational tests of theoretically predicted size distributions and waiting time distributions. Attempts have been undertaken to import physical models into the numerical SOC toy models, such as the discretization of magneto-hydrodynamics (MHD) processes. The novel applications stimulated also vigorous debates about the discrimination between SOC models, SOC-like, and non-SOC processes, such as phase transitions, turbulence, random-walk diffusion, percolation, branching processes, network theory, chaos theory, fractality, multi-scale, and other complexity phenomena. We review SOC studies from the last 25 years and highlight new trends, open questions, and future challenges, as discussed during two recent ISSI workshops on this theme.Fil: Aschwanden, Markus J.. Lockheed Martin Corporation; Estados UnidosFil: Crosby, Norma B.. Belgian Institute For Space Aeronomy; BélgicaFil: Dimitropoulou, Michaila. University Of Athens; GreciaFil: Georgoulis, Manolis K.. Academy Of Athens; GreciaFil: Hergarten, Stefan. Universitat Freiburg Im Breisgau; AlemaniaFil: McAteer, James. University Of New Mexico; Estados UnidosFil: Milovanov, Alexander V.. Max Planck Institute For The Physics Of Complex Systems; Alemania. Russian Academy Of Sciences. Space Research Institute; Rusia. Enea Centro Ricerche Frascati; ItaliaFil: Mineshige, Shin. Kyoto University; JapónFil: Morales, Laura Fernanda. Canadian Space Agency; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nishizuka, Naoto. Japan National Institute Of Information And Communications Technology; JapónFil: Pruessner, Gunnar. Imperial College London; Reino UnidoFil: Sanchez, Raul. Universidad Carlos Iii de Madrid. Instituto de Salud; EspañaFil: Sharma, A. Surja. University Of Maryland; Estados UnidosFil: Strugarek, Antoine. University Of Montreal; CanadáFil: Uritsky, Vadim. Nasa Goddard Space Flight Center; Estados Unido