ArrayExpress Uploader07759arrayexpress_sid6We have previously shown that rheumatoid factors (RF) produced by Fas-deficient autoimmune-prone mice typically bind autologous IgG2a...18025183E-GEOD-6674/profile/8773/arrayexpressuploader015autoimmune diseasechromatincompartmentdiseaseinternalDec.12, 2014Falsetranscription-profiling-of-mouse-am-14-b-cells-stiE-GEOD-6674_A-AFFY-45Transcription profiling of mouse AM-14 B cells stimulated through the B cell receptor (BCR) and/or Toll-like receptors (TLR)Nov.13, 2014We have previously shown that rheumatoid factors (RF) produced by Fas-deficient autoimmune-prone mice typically bind autologous IgG2a with remarkably low affinity. Nevertheless, B cells representative of this RF population proliferate vigorously in response IgG2a/chromatin immune complexes through a mechanism dependent on the sequential engagement of the BCR and Toll-like receptor 9 (TLR9). To more precisely address the role of both receptors in this response, we analyzed the signaling pathways activated in AM14 B cells stimulated with these complexes. We found that the BCR not only serves to direct the chromatin complex to an internal compartment where it can engage TLR9 but also transmits a suboptimal signal that in combination with the signals emanating from TLR9 leads to NF?B activation and proliferation. Importantly, engagement of both receptors leads to the upregulation of a group of gene products, not induced by the BCR or TLR9 alone, that include IL-2. These data indicate that autoreactive B cells, stimulated by a combination of BCR and TLR9 ligands, acquire functional properties that may contribute to the activation of additional cells involved in the autoimmune disease process. Experiment Overall Design: 15 Samples, 3 replicates for each treatmenthttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-6674mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-6674/samples/