Id3 Orchestrates Germinal Center B Cell Development

Previous studies have demonstrated that E-proteins induce AID expression in activated B cells. Here we have examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B-lineage cells but declines in GC cells. Immunized mice depleted for Id3 expression displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class switched cells, were associated with decreased antibody titers and lower numbers of plasma cells. In vitro Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding for signaling components of antigen receptor, cytokine receptor and chemokine receptor mediated signaling was significantly impaired. We propose that during the GC reaction Id3 levels decline to activate the expression of genes encoding for signaling components that mediate B cell receptor and or cytokine-mediated signaling to promote the differentiation of GC B cells. Overall design: B cells derived from control and CD19-Cre;Id3loxP/loxP mice were activated in vitro in the presence of LPS and IL-4 for 24 or 48 hours. RNA was isolated from naïve as well as activated control and CD19-Cre;Id3loxP/loxP mice and analyzed by RNA-seq, in duiplicate.