FRZB, WNT3, 5A, 10 were changed to a lesser e tent by IgM. This is an important observation because Wnt5a produced by fol licular dendritic cells affects the B cell differentiation program of germinal centre B cells. The e pression of FZD6 and WNT5a are modulated by IL21 and TLE3 by LPS. In addition, CD40L modulates the e pression of FRZB, KREMEN2, TCF7, TLE3 and WNT5A. Therefore, we conclude that IgM stimulation affects major signature genes such as MYC and LEF1 defining the inde of Burkitt likeness. IL21, CD40L, IgM, BAFF and LPS affected gene e pression changes similarity and uniqueness In order to describe similarities in gene e pression the global responses to the stimuli were analysed by the Ordered List approach. In this approach, genes were ranked according to their fold change in re sponse to respective stimulation.

Pairwise comparisons of top and bottom ranks of lists representing IL21, CD40L, IgM, BAFF and LPS responses were plotted. We observed a high overlap of genes responding in the same manner for each Batimastat pairwise comparison. This can be seen in Figure 3 by the difference between the blue line, representing the number of overlapping genes at the corresponding position of the gene lists given and the orange area giving the e pected size of a random overlap. The gene lists are also compared in reversed order represented by the green line. The genes are summarized within the supplementary information. The strongest overlap was observed for IL21 and IgM.

This is somehow surprising since it was sug gested that the shared NF��B driven gene e pression changes mediated by LPS, CD40L, IgM or BAFF would be dominant in defining the major pattern of gene e pres sion changes. However, the strong overlap of IL21 with IgM is also reflected in the GO analysis, showing that IL21 and IgM gene e pression changes are enriched for positive regulation of the I��B kinase NF ��B cascade, RNA metabolic processes or immune system processes but also DNA repair. The shared functions of CD40L and IgM affected genes are for e ample characterized by immune response, antigen processing and presentation or positive regulation of B cell activation, BMP signalling pathway and phosphate meta bolic processes. In addition, we describe genes that are specifically affected only by one of the utilized stimuli.

Interestingly, those genes which are dominantly affected by IgM treatment are part of biological processes such as nucleic acid binding, PI3K regulator activity, regulation of cell cycle or meta bolic processes, Wnt receptor signalling pathways and response to hypo ia. Therefore, our data now provide a comprehensive col lection of gene e pression changes induced by different physiological stimuli. These data sets can be used for a better understanding of gene e pression changes in B cell signalling and lymphoma as we will show below. An in vitro model system will be tested to investigate path way activations in individual DLBCL. Coherent gene e pression of IgM affected g