IgD expressed in nucleus of Pro-B cells promotes Pro-B cells proliferation by regulating E2F3 expression [ChIP-seq]

Immunoglobulin D (IgD) has historically been considered as a surface marker of mature B cell with its specific function being undefined. Until now, no evidence had been presented to suggest that IgD is also expressed in pro-B cells. Here, we developed a mouse model with a targeted deletion of IgD, and assessed the production of the IgM, IgG and IgA, as well as the generation of the antigen specific antibodies. The findings indicated no significant differences in these Ig levels between wild type and IgD-deficient mice. However, we observed a notable reduction in the number of mature B cells, which led us to the surprising discovery that this decrease in B cell count begins at the pro-B cell stage. More significantly, we identified that IgD, in its intact tetrapeptide structure, is expressed in the nucleus of pro-B cells. Functionally, IgD appears to promote the proliferation of pro-B cells. Mechanically, IgD exhibits a transcription factor-like activity, and directly binds to the promoter region of E2f3, a pro-proliferative transcription factor. IgD drives the expression of E2f3, thereby promoting the proliferation of pro-B cells. This novel insight into the physiological significance of IgD in B cell development has important implications for our understanding of immune system function.