B lymphocytes and the antibodies they produce play a critical role in host defense against microbes and in autoimmune diseases. A hallmark of adaptive immunity is heterogeneity of cell fate among antigen-experienced B cells. Substantial preliminary data suggest B cells can diversify the fates and functions of their daughter cells using an evolutionarily conserved strategy to allocate unequal amounts of key components. This project will test whether asymmetric cell division is a cardinal feature of the early B cell-mediated immune response.
The aims will examine whether a deterministic mechanism is used to diversify the initial class switch choices of sibling B cells, and whether asymmetric division i used to meet the opposing demands of terminal differentiation and self-renewal. This project will also examine whether ancestral regulators of cell polarity are responsible for establishing cell biological features necessary for asymmetric division, and how asymmetrically inherited proteins could mediate fate disparity in daughter B cells. These studies should provide a framework for rational engineering of immune responses and vaccines against microbial agents and address fundamental uncertainties regarding the principle of clonal selection of lymphocytes in response to infectious diseases or during situations when our immune cells attack our own selves.
B lymphocytes are specialized white blood cells that protect us against infection. These cells need to be able to replenish themselves for vaccines to work properly. This project will provide important information about how these cells provide long-term immunity after we are vaccinated.
|Yen, Bonnie; Fortson, Katherine T; Rothman, Nyanza J et al. (2018) Clonal Bifurcation of Foxp3 Expression Visualized in Thymocytes and T Cells. Immunohorizons 2:119-128|
|Kratchmarov, Radomir; Viragova, Sara; Kim, Min Jung et al. (2018) Metabolic control of cell fate bifurcations in a hematopoietic progenitor population. Immunol Cell Biol 96:863-871|
|Kratchmarov, Radomir; Magun, Arthur M; Reiner, Steven L (2018) TCF1 expression marks self-renewing human CD8+ T cells. Blood Adv 2:1685-1690|
|Chen, Yen-Hua; Kratchmarov, Radomir; Lin, Wen-Hsuan W et al. (2018) Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway. Cell Rep 22:860-868|
|Kratchmarov, Radomir; Nish, Simone A; Lin, Wen-Hsuan W et al. (2017) IRF4 Couples Anabolic Metabolism to Th1 Cell Fate Determination. Immunohorizons 1:156-161|
|Nish, Simone A; Zens, Kyra D; Kratchmarov, Radomir et al. (2017) CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions. J Exp Med 214:39-47|
|Adams, William C; Chen, Yen-Hua; Kratchmarov, Radomir et al. (2016) Anabolism-Associated Mitochondrial Stasis Driving Lymphocyte Differentiation over Self-Renewal. Cell Rep 17:3142-3152|
|Lin, Wen-Hsuan W; Nish, Simone A; Yen, Bonnie et al. (2016) CD8+ T Lymphocyte Self-Renewal during Effector Cell Determination. Cell Rep 17:1773-1782|
|Lin, Wen-Hsuan W; Adams, William C; Nish, Simone A et al. (2015) Asymmetric PI3K Signaling Driving Developmental and Regenerative Cell Fate Bifurcation. Cell Rep 13:2203-18|
|Paley, Michael A; Gordon, Scott M; Bikoff, Elizabeth K et al. (2013) Technical Advance: Fluorescent reporter reveals insights into eomesodermin biology in cytotoxic lymphocytes. J Leukoc Biol 93:307-15|
Showing the most recent 10 out of 17 publications