FCER2A’s up-regulation might have been expected most on B-cells undergoing class-switching of antibody isotypes, and therefore activation. However, the relationships AbMole Clofentezine between FCER2A and EBI-2 made clear how the opposite effect may arise. FCER2A is specifically up-regulated in response to EBI-2 expression, and meanwhile, EBI-2 expression is actively down-regulated among germinal center B-cells, the B-cells most actively undergoing hyper-proliferation and hypermutation. The anti-correlation observed between FCER2A expression and somatic mutation is therefore able to emerge from an indirect, but distinctly negative, relationship between the two. The correlations so far discussed were calculated across individual cells. However, one could imagine that clonal relationships might bias results, especially if phenotypic state is inherited during cell division. In order to eliminate this possibility, we used our knowledge of the B-cell population’s clonal relationships from their antibody sequences. By iteratively and randomly sampling cells from each clonal lineage, we ensured each would be equally represented in the final, averaged, correlation calculation. The resulting correlation values were qualitatively the same as those performed across cells individually. Clonal relatedness did not therefore play a significant part in defining the observed gene expressionmutation correlations. These relationships were therefore found to represent independently-sampled gene expression programs. Iterative, independent sampling of cells across each clonal antibody lineage allowed us to calculate Spearman rank-permutation p-values across the data-set for each mutation/geneexpression relationship. Broad significance was observed among the genes correlating most positively and most negatively with somatic mutation. Its consistently significant correlation with mutations may suggest an active strengthening of a B-cell’s ability to check the efficacy of mutagenesis that is coincident with the accumulation of the mutations themselves. This suggested their regulation was among the most strongly coupled to antibody proteindiversification. Surprisingly, however, the magnitudes of the differences between non-synonymous and synonymous mutation/gene-expression correlations were very different between the two mice.This stood in sharp contrast to the similarity between the magnitudes of mutation/gene-expression correlations themselves. The adaptive immune system selects B-cells that produce highspecificity antibodies to target a wide range of pathogens. Active feedback between induced antibody mutation and its effect on antibody specificity is therefore at the core of a successful immune response. In this paper, we measured this feedback by performing simultaneous measurement of gene-expression and antibody-gene variation across ensembles of individual B-cells, thereby quantifying the co-variance between these two sets of variables.