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Articles 691 - 720 of 838
Full-Text Articles in Biology
Structural, Biophysical, And Functional Studies Of Trem2 In Neurodegenerative Disease, Daniel L. Kober
Structural, Biophysical, And Functional Studies Of Trem2 In Neurodegenerative Disease, Daniel L. Kober
Arts & Sciences Graduate Student Theses and Dissertations
Alzheimer's disease (AD) and other neurodegenerative diseases present a large and growing challenge to global health. The immune system, particularly the innate immune system, is increasingly recognized as having a major role in these pathologies. The innate immune system is responsible to contain disease and promote healing. However, immune misregulation exacerbates disease. The innate immunomodulatory receptor Triggering receptor expressed on myeloid cells-2 (TREM2) is expressed on myeloid cells such as dendritic cells, macrophages, and in the brain, on microglia. TREM2 is a single-pass transmembrane receptor with an extracellular Ig domain that mediates ligand binding. This protein regulates inflammation in vitro …
Regulation Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Kevin Flanagan
Regulation Of The Pro-Tumorigenic Senescence-Associated Secretory Phenotype, Kevin Flanagan
Arts & Sciences Graduate Student Theses and Dissertations
Tumorigenesis results from the convergence of cell autonomous mutations and corresponding stromal changes that promote tumor cell growth. Mutations and stromal changes both accumulate with age and together account for the dramatic increase in cancer incidence with age. One change that occurs with age is the accumulation of stromal senescent cells. Senescent stromal cells secrete pro-tumorigenic factors collectively termed the senescence-associated secretory phenotype (SASP). The SASP impacts every stage of tumorigenesis and is a promising therapeutic target. As such, it is important to understand how the SASP is regulated. Many but not all SASP factors are regulated transcriptionally by NF-kB …
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Mitochondrial Dynamics Controls T Cell Fate Through Metabolic Programming, Michael Buck
Arts & Sciences Graduate Student Theses and Dissertations
Activated effector T (TE) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (TM) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that TE cells have punctate mitochondria, while TM cells maintain fused networks. The fusion protein Opa1 is required for TM, but not TE cells after infection, and enforcing fusion in TE cells imposes TM cell characteristics and enhances antitumor function. Our data suggest that, …
Factors That Contribute To De Novo Protein Misfolding And Prion Formation In Saccharomyces Cerevisiae, Kathryn Morgan Keefer
Factors That Contribute To De Novo Protein Misfolding And Prion Formation In Saccharomyces Cerevisiae, Kathryn Morgan Keefer
Arts & Sciences Graduate Student Theses and Dissertations
Protein misfolding is a common phenomenon that can have severe consequences on cellular and organismal health. Despite this, the causes of protein misfolding remain poorly understood. Prions are a class of proteins that, when misfolded, can convert other molecules into a heritable, non-native conformation. The yeast Saccharomyces cerevisiae naturally harbors several diverse prion-forming proteins; thus, it is an ideal model with which to investigate the factors that influence misfolding and aggregation.This thesis utilizes the yeast prions [PSI+] and [RNQ+] to investigate two distinct steps of the protein misfolding pathway: interactions with chaperones and their cofactors, and heterologous templating by other …
The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann
The Role Of Rna Interference In The Control Of Leishmania Rna Virus 1 Infection, Erin Acino Brettmann
Arts & Sciences Graduate Student Theses and Dissertations
The presence of Leishmania RNA virus 1 (LRV1) in parasites of the Leishmania (Viannia) subgenus increases the virulence of the parasite in mouse models of leishmaniasis and is correlated with treatment failure, relapse, and the development of mucocutaneous disease in humans. LRV1 is not shed or infectious; rather, the infection is persistent, and as yet it is unknown how the parasite controls virus levels. Many eukaryotic organisms use RNA interference (RNAi) to limit virus replication, and Leishmania (Viannia) parasites have an active RNAi pathway. To determine whether Leishmania are capable of using RNAi to control LRV1, we sequenced sRNAs from …
The Effects Of The Gut Microbiota On The Host Chromatin Landscape, Nicholas Semenkovich
The Effects Of The Gut Microbiota On The Host Chromatin Landscape, Nicholas Semenkovich
Arts & Sciences Graduate Student Theses and Dissertations
The human gut microbiota is home to tens of trillions of microbes belonging to all three domains of life. The structure and expressed functions of this community have myriad effects on host physiology, metabolism, and immune function. My studies focused on a facet of host-microbial interactions and mutualism that has not been explored to a significant degree in part because of the absence of suitable tools: namely, if, when, and how the gut microbiota produces durable effects on host biology through its impact on the epigenome. To address this area, I turned to gnotobiotic mice and developed a variety of …
Biophysical Studies Of The Intracellular Domains Of The Egfr Family Of Receptor Tyrosine Kinases, Kwabena A N Sarpong
Biophysical Studies Of The Intracellular Domains Of The Egfr Family Of Receptor Tyrosine Kinases, Kwabena A N Sarpong
Arts & Sciences Graduate Student Theses and Dissertations
The epidermal growth factor receptor and its three orthologues, HER2, HER3 and HER4 have been the subject of intensive basic, clinical and translational research due to their involvement in cancers. These proteins are part of elaborate networks that interact with a myriad of other molecules to effect diverse signaling pathways and affect cellular processes such as migration, apoptosis, cell differentiation and so on. In addition to the formation of preformed dimers, it is well established that ligand engagement leads to receptor dimerization in all family members, except HER2. In the past decade, it has been shown that their intracellular domains …
Epigenetic Activation Of The Mouse T Cell Receptor Beta Recombination Center, Jiangyang Zhao
Epigenetic Activation Of The Mouse T Cell Receptor Beta Recombination Center, Jiangyang Zhao
Arts & Sciences Graduate Student Theses and Dissertations
Lymphocytes are the work horses of adaptive immunity. Compared to the B lymphocyte lineage, early stage progenitors of T lymphocytes maintain considerable potential for differentiation into other hematopoietic lineages. T lineage commitment requires the continuous coordination of transcription factors (TFs) by Notch1 signaling after multi-potent progenitors (MPPs) migrate to thymus. One of the first hall marks of T lineage commitment is expression of the T cell receptor β (TCRβ), which is encoded by the Tcrb locus following its assembly by V(D)J recombination, a somatic shuffling of the genome that joins one V, one D, and one J gene segment. Tcrb …
Functional Brain Organization In Space And Time, Timothy Laumann
Functional Brain Organization In Space And Time, Timothy Laumann
Arts & Sciences Graduate Student Theses and Dissertations
The brain is a network functionally organized at many spatial and temporal scales. To understand how the brain processes information, controls behavior and dynamically adapts to an ever-changing environment, it is critical to have a comprehensive description of the constituent elements of this network and how relationships between these elements may change over time. Decades of lesion studies, anatomical tract-tracing, and electrophysiological recording have given insight into this functional organization. Recently, however, resting state functional magnetic resonance imaging (fMRI) has emerged as a powerful tool for whole-brain non-invasive measurement of spontaneous neural activity in humans, giving ready access to macroscopic …
Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures
Mitochondrial Damage Accumulation In Oocytes – A Potential Link Between Maternal Obesity And Increased Cardiometabolic Disease Risk In Offspring., Anna Louise Boudoures
Arts & Sciences Graduate Student Theses and Dissertations
The developmental origins of health and disease (DoHAD) hypothesis suggests that negative maternal lifestyle choices, such as obesity, affect the health of her offspring. Clinical and laboratory studies support this hypothesis – offspring born to obese mothers are at increased risk for health conditions including cardiometabolic syndrome and congenital abnormalities. Maternal obesity damages the oocytes, contributing to the increased disease risk by transmitting damaged organelles and epigenetic modifications to the offspring. Mitochondria, the most abundant organelle in the oocyte, are damaged in oocytes from obese females. However, we do not understand if mitochondrial damage in oocytes is reversible nor why …
Genetic And Genomic Dissections Of Myelinating Glial Cell Development, Breanne Leigh Harty
Genetic And Genomic Dissections Of Myelinating Glial Cell Development, Breanne Leigh Harty
Arts & Sciences Graduate Student Theses and Dissertations
Myelin is a multilamellar sheath made by specialized glial cells that iteratively spiral and compact their plasma membranes around axon segments. In vertebrate nervous systems, myelination facilitates rapid action propagation and provides trophic support critical for neuronal survival. In the central nervous system (CNS), oligodendrocytes (OLs) extend many processes to simultaneously ensheath multiple axons, while in the peripheral nervous system (PNS), myelinating Schwann cells (SCs) pair 1:1 with a single axon segment. Elaboration of the myelin sheath is one of the most exquisite and complex examples of massive coordinated cellular shape changes in the vertebrate nervous system. Furthermore, the importance …
Epigenetic Regulation Of Lymphocyte Development And Transformation, Yue Huang
Epigenetic Regulation Of Lymphocyte Development And Transformation, Yue Huang
Arts & Sciences Graduate Student Theses and Dissertations
Cell identity and function rely on intricately controlled programs of gene regulation, alterations of which underlie many diseases, including cancer. Epigenetic analyses of normal and diseased cells have started to elucidate different facets of epigenetic mechanisms for gene regulation. These include changes in nucleosome density, histone modifications, factor binding and chromosomal architecture. All of these aspects contribute to the activities of regulatory elements conferring promoter, enhancer and insulator functions and the cis-regulatory circuits formed by these elements. Despite this progress, an urgent need remains to profile these features and to study how they cooperatively function in normal and pathogenic settings. …
Mechanisms Of G Protein Regulation By Rgs Proteins And Small Molecule Inhibitors, Stanley Michinobu Kanai
Mechanisms Of G Protein Regulation By Rgs Proteins And Small Molecule Inhibitors, Stanley Michinobu Kanai
Arts & Sciences Graduate Student Theses and Dissertations
G protein coupled receptors transduce diverse extracellular signals like hormones, neurotransmitters, and photons to specific cellular responses through heterotrimeric G proteins. G proteins activate numerous effectors and signal transduction pathways, and therefore the regulation of G proteins is crucial for faithful propagation of specific cellular and physiological responses. A better understanding of the mechanisms that regulate G proteins should provide new insight into signaling pathways that govern healthy and disease states, and also provide opportunities for discovery of novel therapeutic targets.Regulator of G protein signaling (RGS) proteins are crucial regulators of G proteins, for they control amplitude and duration of …
The Rpl13a Snorna U33 Forms Novel Snornps During Lipotoxicity, Miquia Sherree Henderson
The Rpl13a Snorna U33 Forms Novel Snornps During Lipotoxicity, Miquia Sherree Henderson
Arts & Sciences Graduate Student Theses and Dissertations
Lipid overload contributes to the pathogenesis of diabetic complications, causing tissue damage and cell death in a number of organ systems. This process is termed lipotoxicity. Animal and cell culture studies have demonstrated that oxidative stress and endoplasmic reticulum stress are major pathways engaged in the lipotoxic response. However, the molecular mechanisms of lipotoxicity are not well understood. A genetic screen revealed that small nucleolar RNAs (snoRNAs) encoded in the introns of the Rpl13a locus are critical for cell death in response to lipotoxicity. Initial studies have suggested that the Rpl13a snoRNAs function in this pathway through non-canonical modes of …
Beta-Diversity Patterns And Community Assembly Across Latitudes, Emma Moran
Beta-Diversity Patterns And Community Assembly Across Latitudes, Emma Moran
Arts & Sciences Graduate Student Theses and Dissertations
A major goal of community ecology is in understanding variation in community composition, generally termed β-diversity. This variation can result from a variety of mechanisms, including deterministic factors, wherein species sort along biotic or abiotic gradients; stochastic processes, whereby random fluctuations in population sizes cause variation in community composition; and/or dispersal limitation. Although all of these processes are likely occurring in all biological communities, a key question in community ecology research is if their relative importance may vary systematically across environmental or biogeographic gradients. In this dissertation, we combine both observational and experimental research to investigate β-diversity across a biogeographic …
Metabolic Regulation Of Cd8 T Cell Functions In The Tumor Microenvironment, Jing Qiu
Metabolic Regulation Of Cd8 T Cell Functions In The Tumor Microenvironment, Jing Qiu
Arts & Sciences Graduate Student Theses and Dissertations
Failure of T cells to protect against cancer is thought to result from lack of antigen recognition, chronic activation, and/or suppression by other cells. Using a mouse sarcoma model, we show that glucose consumption by tumors metabolically restricts T cells in the tumor microenvironment, leading to their dampened mTOR activity, glycolytic capacity, and IFN-γ production, and thereby allowing tumor progression. We demonstrate that enhancing glycolysis in an antigenic ‘regressor’ tumor is sufficient to override the ability of T cells to respond to a major tumor rejection antigen, allowing progression of tumors that are normally rejected. Checkpoint blockade therapy is used …
The Role Of Histidine Rich Protein Ii In Cerebral Malaria, Priya Pal
The Role Of Histidine Rich Protein Ii In Cerebral Malaria, Priya Pal
Arts & Sciences Graduate Student Theses and Dissertations
Human malaria is caused by five species of Plasmodium. Of these, P. falciparum is the deadliest and is the only species that causes cerebral malaria (CM). CM is a disease of the vascular endothelium characterized by parasite sequestration, increased inflammatory cytokine production, vascular leakage and leukocyte infiltration. A distinguishing feature of P. falciparum infection is the parasite’s production and secretion of histidine-rich protein II (HRPII). HRPII accumulates to high concentrations (up to 100 µg/ml) in serum, which correlates with disease severity. Due to high serum levels of this protein, HRPII has classically been considered a biomarker for P. falciparum infection. …
The Role Of Bhlhe40 In Autoimmune Neuroinflammation And Mycobacterial Infection, Chih-Chung Lin
The Role Of Bhlhe40 In Autoimmune Neuroinflammation And Mycobacterial Infection, Chih-Chung Lin
Arts & Sciences Graduate Student Theses and Dissertations
The mammalian immune system is composed of innate and adaptive compartments, which cooperate with each other to maintain homeostasis and protect the host from the invasion by a variety of pathogens. The tight control of immune responses is extremely important for all individuals. Here, we discovered that the transcription factor basic helix-loop-helix family, member e40 (Bhlhe40) is a critical protein that regulates the autoimmune ("against self") and anti-microbial ("against non-self") responses of myeloid cells and T lymphocytes. Multiple sclerosis (MS) is a human neuroinflammatory disease in the central nervous system with an autoimmune etiology. We have reported that Bhlhe40 positively …
Modeling Complex Patterns Of Differential Dna Methylation That Associate With Expression Change, Christopher E. Schlosberg
Modeling Complex Patterns Of Differential Dna Methylation That Associate With Expression Change, Christopher E. Schlosberg
Arts & Sciences Graduate Student Theses and Dissertations
Gene expression is driven by specific combinations of transcription factors binding to regulatory sequences to define cell type expression profiles. Changes in DNA sequence alter transcription factor binding affinities and gene expression, and DNA methylation is an additional source of variation that is maintained throughout cellular division. Numerous genomic studies are underway to determine which genes are abnormally regulated by DNA methylation in disease. However, we have a poor understanding of how disease-specific methylation variation affects expression. Global DNA demethylation agents have been clinically approved for use in cancer, which has spurred interest in identifying genes which would be most …
Defining The Ontogeny And Functions Of Macrophages In Pancreatic Ductal Adenocarcinoma, Yu Zhu
Defining The Ontogeny And Functions Of Macrophages In Pancreatic Ductal Adenocarcinoma, Yu Zhu
Arts & Sciences Graduate Student Theses and Dissertations
The immune system plays an essential role in protecting the host organisms against both foreign invaders and self-attacks arisen within the host, such as tumors. Instead of promoting the long-term fitness of the organism, the immune system is often suppressed or hijacked by tumor cells to accelerate the progression of malignancies. Among the key drivers of immune suppression, macrophages are one of the most abundant immune cells present in tumor tissues. High levels of macrophage infiltration in the malignant tissues correlate with negative patient outcome in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), one of the most lethal …
Novel Regulation Of The Nonsense-Mediated Rna Decay Pathway, Andrew Keith Nickless
Novel Regulation Of The Nonsense-Mediated Rna Decay Pathway, Andrew Keith Nickless
Arts & Sciences Graduate Student Theses and Dissertations
The nonsense mediated RNA decay (NMD) pathway maintains the integrity of cellular RNAs and controls gene expression. NMD is essential for vertebrate development and defects in NMD are associated with a variety of neurodevelopmental disorders and cancers. NMD activity is tightly regulated and is altered in response to environmental and developmental signals. To better study this dynamic pathway and to identify clinically relevant regulators of its activity, we developed a dual-color bioluminescent NMD reporter that rapidly and accurately quantifies NMD activity in mammalian cells. Using this reporter, we performed a chemical screen for small-molecule modulators of NMD activity and identified …
Regulation Of Mycobacterial Transcription Initiation, Jayan Rammohan
Regulation Of Mycobacterial Transcription Initiation, Jayan Rammohan
Arts & Sciences Graduate Student Theses and Dissertations
Cellular life relies on gene expression, in which DNA is first transcribed into RNA, which is then translated into protein. Transcription is performed by the protein RNA polymerase (RNAP), which interacts with DNA in three sequential events known as initiation, elongation and termination. Mycobacterium tuberculosis (Mtb) represents a global burden to public health, and the transcription factors CarD and RbpA are both essential to Mtb. I have studied the effect of CarD and RbpA on transcription initiation in vitro at the Mtb rrnAP3 promoter. I have shown that CarD stabilizes unwinding of promoter DNA by RNAP using a two-tiered kinetic …
Discovery And Characterization Of A Novel Class Of Metabolic Regulators In The Malaria Parasite Plasmodium Falciparum, Ann Marie Guggisberg
Discovery And Characterization Of A Novel Class Of Metabolic Regulators In The Malaria Parasite Plasmodium Falciparum, Ann Marie Guggisberg
Arts & Sciences Graduate Student Theses and Dissertations
The malaria parasite, Plasmodium falciparum, infects hundreds of millions of people per year and causes hundreds of thousands of deaths. Within the host red blood cell, the parasite relies on glycolysis for energy and synthesis of essential biomolecules. One such anabolic fate of glucose is the synthesis of isoprenoids, a broad and essential class of compounds that participate in a variety of cellular functions. In the face of ever-evolving drug resistance, new inhibitors and better understanding of parasite metabolism are required. The antibiotic fosmidomycin (FSM) targets the methylerythritol phosphate pathway for isoprenoid synthesis and is a well-validated inhibitor of P. …
Genetic Mechanisms For The Maintenance Of Behavioral Mating Barriers In Drosophila, Kathleen M. Mortland
Genetic Mechanisms For The Maintenance Of Behavioral Mating Barriers In Drosophila, Kathleen M. Mortland
Arts & Sciences Graduate Student Theses and Dissertations
One of the most successful and diverse systems involved in the maintenance of behavioral barriers between closely related animal species is pheromonal communication. In the fruit fly, contact chemosensation input is especially important during sexual decision-making as it allows for the sensing of sex and species-specific non-volatile cuticular hydrocarbons (CHCs), which function as insect pheromones. However, how pheromonal systems support the maintenance of mating barriers is puzzling since any change in either pheromone ligands or their cognate receptors would carry a fitness cost, which should be eliminated by stabilizing selection. To resolve this evolutionary conundrum I hypothesized that pleiotropic genes …
A Study On The Role And Regulation Of The Na+-Leak Channel, Non-Selective (Nalcn) In Myometrial Function, Erin Lynn Reinl
A Study On The Role And Regulation Of The Na+-Leak Channel, Non-Selective (Nalcn) In Myometrial Function, Erin Lynn Reinl
Arts & Sciences Graduate Student Theses and Dissertations
Uterine contractions are tightly regulated throughout pregnancy, remaining relatively quiescent for the majority of pregnancy to promote fetal development, while becoming highly activated at term to effectively expel the fetus. Contractions are coordinated through electrical and mechanical coupling of myometrial smooth muscle cells (MSMCs). Ion channel activity, which alters the electrical activity of MSMCs, can directly affect the contraction profile. Thus there is great interest in the field of reproduction to understand which ion channels regulate uterine excitability, and particularly how they may enable the transition from uterine quiescence to uterine activation for labor. The focus thus far has been …
Structure, Dynamics, And Regulation Of Collective Cell Migration, Andrew J. Loza
Structure, Dynamics, And Regulation Of Collective Cell Migration, Andrew J. Loza
Arts & Sciences Graduate Student Theses and Dissertations
Collective migration is the process by which cells organize individual motions to productively migrate as a group and plays a fundamental role in organism development, tissue regeneration, and cancer invasion. In development, coordinated migration facilitates the formation of complex organ structures and is required for proper dissemination of neural crest cells throughout an organism. After injury, this process allows breaches in epithelial layers to be repaired while maintaining tissue integrity, and in cancer, collective behavior enhances invasion of tumor cells into the surrounding tissue. Chapter 1 provides an introduction for the role of collective migration across an organism’s lifespan, the …
Epigenomics Of Cell Fate In Development And Disease, Rebecca Faith Lowdon
Epigenomics Of Cell Fate In Development And Disease, Rebecca Faith Lowdon
Arts & Sciences Graduate Student Theses and Dissertations
Epigenetic features at regulatory elements provide instructive cues for transcriptional regulation during development. However, the particular epigenetic alterations necessary for proper cell fate acquisition and differentiation are not well understood. This dissertation explores the epigenetic dynamics of regulatory elements during development and uses epigenome annotations to document inappropriate transcriptional regulation in disease. First, I summarize my contributions to developing a new algorithm for detecting differential DNA methylation, M&M. I report the application of the M&M algorithm to identify distinct classes of DNA methylation dynamics in surface ectoderm (SE) progenitor cells and SE-derived lineages: epigenome alterations, and differential DNA methylation in …
Discovery And Functional Implication Of Genetic Alterations Associated With Clonal Hematopoietic Expansion, Mingchao Xie
Discovery And Functional Implication Of Genetic Alterations Associated With Clonal Hematopoietic Expansion, Mingchao Xie
Arts & Sciences Graduate Student Theses and Dissertations
Cancers, including hematologic malignancies, arise as a result of the stepwise accumulation of mutations. Some early mutations that potentially initiate clonal expansion might exist in patients many years before they develop obvious disease symptoms. Therefore, identifying and characterizing these early mutations are critical to understanding the genetic basis of tumorigenesis. Here, we analyzed blood-derived DNA sequencing data from 2,728 individuals without apparent hematologic malignancies and identified 77 blood-specific mutations in 31 cancer-associated genes. Importantly, 83% of all mutations occurred in 19 genes that have been previously linked to hematological malignancies, such as DNMT3A, TET2, JAK2, and ASXL1. By investigating these …
The Human Arf Tumor Suppressor Regulates Drosha Nucleolar Localization And Rrna Processing Activity, Sree Chandana Sridhar Yaddanapudi
The Human Arf Tumor Suppressor Regulates Drosha Nucleolar Localization And Rrna Processing Activity, Sree Chandana Sridhar Yaddanapudi
Arts & Sciences Graduate Student Theses and Dissertations
Ribosomes are vital to the survival of a cell, as they are directly responsible for the synthesis of proteins, which perform critical cellular functions. As such, majority of the energy reserves in a proliferating cell are expended towards synthesis of ribosomes. Cancer cells, with their enhanced proliferation rates, tend to upregulate ribosome biogenesis in order to meet the demand for increased protein synthesis necessary to sustain rapid proliferation. Many of the oncogenes and tumor suppressors known to be deregulated in cancers are capable of positively and negatively regulating ribosome biogenesis, respectively. The ARF tumor suppressor strongly suppresses ribosome biogenesis, particularly …
Regulation Of Durable Adaptive Immune Response By The C-Myc-Ap4 Transcriptional Cascade, Chun Chou
Regulation Of Durable Adaptive Immune Response By The C-Myc-Ap4 Transcriptional Cascade, Chun Chou
Arts & Sciences Graduate Student Theses and Dissertations
The process of amplifying immune responses by expanding a small number of antigen-specific cells, termed clonal expansion, is an important feature of the adaptive immunity. Whereas clonal expansion of cytotoxic T lymphocytes is required for complete eradication of intracellular pathogens, proliferation of B lymphocytes in the germinal centers (GC) is critical for generating a diverse immunoglobulin gene repertoire from which protective antibody carrying multiple mutations can arise. While the proto-oncogene c-MYC is absolutely required for the activation and cell cycle initiation in lymphocytes, its expression is temporally restricted. Activated lymphocytes, however, continue to proliferate after c-MYC levels decay to maximize …