New roles for Id3 in B and T cell development
- Author(s): CHEN, Shuwen
- Advisor(s): Murre, Cornelis
- et al.
E proteins have been shown to play an important role during various stages of B and T cell development. E proteins execute this regulatory function mainly via binding to the E-box sequence around the target genes. However, the activity of E proteins can be inhibited by Id proteins, such as Id2 and Id3 in the immune system.
Previous studies have suggested crucial roles played by Id2 and Id3 in the differentiation process of certain T cell lineages. Id2 was required for CD8 T cell differentiation and activation, while Id3 was required to inhibit E2A activity upon pre-TCR and TCR signaling. During my PhD study, I performed a wide array of experiments to probe into the functions of Id2 and Id3 during the development of regulatory T cells (Treg) and innate-like follicular helper T (Tfh) cells. My work helped unveil that Id2 and Id3 expression was required for Treg cells to suppress the onset of fatal Th2-mediated inflammation. Meanwhile, I also discovered that thymic Id2 and Id3 expression was indispensable for inhibiting the expansion of innate-like Tfh cells and the pathogenesis of αβ T cell lymphoma.
Besides T cells, B cells are also a target population to be regulated by Id proteins like Id3. Ablating Id3 expression specifically in the B cells, I found that these Id3-deficient B cells were clearly impaired in their ability to differentiate into germinal centers upon antigen stimulation. In addition, without Id3 expression, these B cells can no longer elicit any IgG1 response during the memory phase upon encountering a secondary challenge.
To summarize, my PhD study helped to reveal the important functions played by Id2 and Id3 during the differentiation and activation of different lymphocytes.