The regulation of Immune cell differentiation unit(Haikun Wang)
Production of high affinity and long-lived antibodies by immune cells is critically essential for protection against infectious diseases, and it is also the foundation of most effective vaccines. Our research aims to understand transcriptional regulation in the development and function of Follicular Helper T (TFH) cells and B cells, two key components of humoral immunity. Knowledge obtained in our studies will facilitate new vaccine development, meanwhile offering new strategies for the treatment of infectious diseases such as HIV and influenza.
1. Transcriptional regulation in TFH cells development.
Follicular helper T cells (TFH cells) are a specialized CD4+ T cell subset that provides B cell help for germinal center formation. TFH cells are characterized by the expression of surface molecules that facilitate functional interactions with B cells such as the chemokine receptor CXCR5, ICOS and PD-1. The transcription factor Bcl-6 is a central regulator of TFH cell differentiation, and the cytokine interleukin 21 is a key cytokine for both TFH and germinal center B cell differentiation. Although the essential function of TFH for germinal center formation has been elucidated, how TFH cells differentiate from CD4+ effector T cells remains unclear. We are interested in the key signaling pathways and transcription factors involved in T differentiation and functions.
2. Transcriptional regulation of mature B cell differentiation.
Mature B cell differentiation is also a complex process. After encountering antigen and receiving cognate T cell help, mature B cells form germinal centers in the follicles, where B cells undergo clonal expansion, selection, and differentiation into either memory B cells or plasma cells. At each differentiation step, distinct regulatory networks are engaged to regulate the B cell proliferation, survival and differentiation. Perturbations in B cell differentiation give rise to certain types of lymphoma. Here, we aim to identify novel stage-specific transcriptional networks that regulate mature B cell differentiation, with a particular focus on the molecules that are known to be associated with the pathogenesis of B lymphomas. Built on our past work, our current study will focus on the roles of Foxp1 in mature B cells differentiation and human B cell lymphomas.