Signalling of the BCR is regulated by a lipid rafts-localised transcription factor, Bright.

Regulation of BCR signalling strength is crucial for B-cell development and function. Bright is a B-cell-restricted factor that complexes with Bruton's tyrosine kinase (Btk) and its substrate, transcription initiation factor-I (TFII-I), to activate immunoglobulin heavy chain gene transcription in the nucleus. Here we show that a palmitoylated pool of Bright is diverted to lipid rafts of resting B cells where it associates with signalosome components. After BCR ligation, Bright transiently interacts with sumoylation enzymes, blocks calcium flux and phosphorylation of Btk and TFII-I and is then discharged from lipid rafts as a Sumo-I-modified form. The resulting lipid raft concentration of Bright contributes to the signalling threshold of B cells, as their sensitivity to BCR stimulation decreases as the levels of Bright increase. Bright regulates signalling independent of its role in IgH transcription, as shown by specific dominant-negative titration of rafts-specific forms. This study identifies a BCR tuning mechanism in lipid rafts that is regulated by differential post-translational modification of a transcription factor with implications for B-cell tolerance and autoimmunity.

The problem of choice.

Convictions are a driving force for actions. Considering that every individual has a different set of convictions and larger groups act once a consensus decision is reached, one can see that debate is an inherent exercise in decision-making. This requires a sustainably generated surplus to allow time for intellectual exchange, gathering of information and dissemination of findings. It is essential that the full spectrum of options remain treated equally. At the end of this process, a choice has to be made. Looking back at a later time point, a retrospective analysis sometimes reveals that the choice was neither completely free nor a truly conscious one. Leaving the issue of consequences of a once made decision aside, we wish to contribute to the debate of the problem of choice.

Another challenge for scientists.

By nature, scientists contribute to our understanding of nature and ourselves. As communities undergo significant changes, new challenges are presented. Here, we offer alternative views on recent changes in society.

To know or not to know: archiving and the under-appreciated historical value of data.

Surplus goods, produced by a community, allow individuals to dedicate their efforts to abstract problems, while enjoying the benefits of support from the community. In return, the community benefits from the intellectual work, say, efficiently producing goods or profound medical aid. In further elevating quality of life, we need to understand nature and biology on the most detailed level. Inevitably, research costs are increasing along with the need for more scientists to specialize their efforts. As a result, a vast amount of data and information is generated that needs to be archived and made openly accessible with the permission to re-use and re-distribute. With economies undergoing crises and prosperity in an almost cyclic manner, it seems that funding for science and technology follows a similar pattern. Another aspect to the problem of the loss of data is the human propensity, at the level of each individual researcher, to passively discard data in the course of daily life and through a career. In a typical laboratory, significant amounts of information is still stored on disks in file cabinets or on isolated computers, and is lost when a research group disbands. Being conscientious to one's data, to see that it reaches a place in which it can persist beyond the lifespan of any one individual requires responsibility on the part of its creator.