Differential gene expression of the B Cell Receptor (BCR) signaling pathway during pregnancy in mice

Abstract

Abstract The aim of this work was to characterize BCR signaling pathway gene expression in B cells during pregnancy. B-cell receptor (BCR) signaling regulates critical cell-fate decisions in B cells like activation, proliferation, expression of costimulatory molecules and cytokine receptors. Changes on the dynamic of BCR signaling pathway during pregnancy might have an impact on the way how the immune system fight against infections or regulate autoimmunity during this critical period of time. We performed a genome-wide transcriptome profile (GeneChip™ Mouse Gene 1.0 ST Array, Affymetrix) on pure splenic B cells isolated from pregnant and non-pregnant mice. Results were analyzed and significant gene expression regulation was confirmed by qPCR. In silico analysis showed that genes associated with B cell receptor signaling pathway were significantly down-regulated in B cells from pregnant mice compared to non-pregnant animals (≈1.5–2 fold changes, Limma eBayes test, p<0.0001, n=4). Further qPCR analysis showed that genes of the BCR pathway involved in B cell activation, proliferation and antibodies production were down-regulated (Unpaired t test, one-tailed, *p<0.05, n=8) in B cell from pregnant mice as compared to non-pregnant females. In contrast, genes of the BCR pathway that inhibits B cells activation presented no significant differences. We showed here that genes associated with BCR signaling leading to B cell activation and proliferation were significantly down-regulated during pregnancy. These results might help to understand why pregnant women are more susceptible to infections as well as some B cell associated autoimmune diseases experience a significant improvement in the symptoms during pregnancy.