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Immunology and Infectious Disease

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B cell

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The E26 Transformation-Specific-Family Transcription Factor Spi-C Is Dynamically Regulated By External Signals In B Cells, Hannah L. Raczkowski Jul 2021

The E26 Transformation-Specific-Family Transcription Factor Spi-C Is Dynamically Regulated By External Signals In B Cells, Hannah L. Raczkowski

Electronic Thesis and Dissertation Repository

Spi-C is an E26 transformation-specific transcription factor closely related to PU.1 and Spi-B. Spi-C has lineage-instructive functions important in antibody-generating responses, B cell development, and red pulp macrophage generation. Spi-C is inducible by heme- and NF-κB-dependent pathways in macrophages. The present research aimed to examine the regulation of Spi-C in B cells. RT-qPCR revealed that Spic expression was reduced in B cells following addition of lipopolysaccharide, anti-IgM antibodies, CD40L, or cytokines BAFF+IL-4+IL-5. Blocking proliferative signaling partially prevented downregulation of Spic. Unstimulated B cells upregulated Spic over time. To determine the mechanism of Spic regulation, we examined the Spic promoter …


Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain Oct 2018

Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain

Electronic Thesis and Dissertation Repository

Germinal center (GC) responses are responsible for the protection provided by immunizations but can also drive autoimmunity. B and T cells collaborate in the GC to target the same antigen (Ag) to inform B cell differentiation; however, the properties of Ags differ substantially in autoimmunity and foreign-Ag driven immunity. Currently, it is not well understood how properties of the Ag itself influence the initiation or progression of GC responses, limiting our ability to develop effective vaccinations and predict the progression of autoimmune responses. The purpose of this thesis is to assess how GC responses initiate and progress when immunizing with …


The E26 Transformation-Specific Transcription Factors Pu.1, Spi-B, And Spi-C Regulate Transcriptional Activation And Repression Of Nfkb1 To Control B Cell Development And Function, Stephen Ka Ho Li Apr 2015

The E26 Transformation-Specific Transcription Factors Pu.1, Spi-B, And Spi-C Regulate Transcriptional Activation And Repression Of Nfkb1 To Control B Cell Development And Function, Stephen Ka Ho Li

Electronic Thesis and Dissertation Repository

PU.1, Spi-B, and Spi-C are highly related E26 transformation-specific family transcription factors that can bind nearly identical DNA sequences. PU.1 and Spi-B (encoded by Spi1 and Spib respectively) are important for B cell development and function, but the function of Spi-C (encoded by Spic) in B cells is not clear. The objective of this study was to determine PU.1, Spi-B, and Spi-C’s function during B cell development, and during TLR-mediated responses. It was hypothesized that PU.1 and Spi-B were required for positively regulating components of TLR responses, and Spi-C inhibited PU.1 and Spi-B targets. Spi1+/-Spib-/- ( …