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Transcriptional regulation of antibody responses; implications for protective immunity and disease development (#202001)

About This PhD Project

Project Description

Plasma cells (PCs) are terminally differentiated B cells that are committed to the secretion of large quantities of antibodies. While this process is essential for the clearance of acute infection and for the generation of long lasting protective immunity, it could also result with the onset of pathogenic antibodies and the development of chronic diseases such as rheumatoid arthritis, multiple sclerosis and cancer. There is therefore considerable interest in defining specific factors and mechanisms that control the development of these cells.

We have recently identified a novel transcriptional factor that suppresses PC differentiation, thereby limits excessive antibody responses (manuscript in preparations). The current project will build on these findings 1) to explore the relative contribution of this factor to progression of various disease models in mice and 2) to investigate the molecular mechanisms involved. Findings from these studies will not only improve our basic understanding of B cell biology, but may also help in the development of novel vaccines and treatments to chronic diseases.

Training Opportunities

In this project we focus is on mechanisms that regulate differentiation of B cells into plasma cells. Better understanding of this process is critical not only for improving our understanding of protective immunity and autoimmune disorders, but also for our ability to control proliferation of B cells, a critical factor in the development of B cell derived cancers. It is therefore suitable for a student that has keen interest in basic immunology and is excited about testing practical biological questions in vitro and in vivo using mouse models. The project will involve a variety of methods with a combination of functional, biochemical and genomic approaches (such as RNA-Seq, ATAC-Seq, ChIP-Seq). Interested candidates are encouraged to contact Dr. Tal Arnon by email directly.

Key Publications

Reboldi A, Arnon TI, Rodda LB, Atakilit A, Sheppard D and Cyster JG. B cell interaction with subepithelial dendritic cells in Peyer's patches is critical for IgA production. (2016) Science 352(6287).

Arnon TI, Horton BM, Grigorova IL and Cyster JG. Visualization of splenic marginal zone B cell shuttling and follicular B cell egress. (2013) Nature 493(7434):684-8.

Weiss M, Byrne AJ, Blazek K, Saliba DG, Pease JE, Perocheau D, Feldmann M, Udalova IA. IRF5 controls both acute and chronic inflammation. (2015) PNAS 1;112(35):11001-6.

Related Subjects

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