The Role of Extracellular Signal-regulated Kinase 2 (ERK2) in Peripheral B Cell Activation and Differentiation

Date
2021
Authors
Negron, Austin Joseph
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Abstract

Activation and differentiation of B cells into antibody-secreting cells (ASCs) is a critical aspect of disease prevention, namely through the provision of protective antibodies against infectious diseases. Additionally, ASCs that migrate to specialized survival niches, such as the bone marrow, where they can persist for years. These cells, known as long-lived plasma cells (LLPCs), provide a constant layer of protection, and thereby represent a core component of immune memory. Importantly, dysregulation of this process is known to underlie certain autoimmune diseases such as Grave's disease or myasthenia gravis, as well as cancers such as multiple myeloma (MM). Therefore, deciphering the molecular mechanisms that govern the fate decisions following B cell activation could potentially lead to more effective treatments for these and other B cell-mediated pathologies. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are effectors of the mitogen-activated protein kinase (MAPK) pathway known to regulate the development, activation, and survival of B cells. Despite sharing extensive structural homology with ERK1, several functions are uniquely attributed to ERK2. Notable among these, ERK2 promotes mitochondrial fission and glycolytic metabolism, which are dynamically regulated during ASC differentiation. Using a mouse model that circumvents the embryonic lethality of a germline Erk2-deletion while allowing the detection of these cells using a fluorescent reporter, our studies show that ERK2 is a key derminant of ASC survival through the regulation of mitochondrial dynamics. These studies offer ERK2 as a potential target towards the treatment of B cell-mediated pathologies.

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Keywords
Antibody-secreting cells, B cells, Calcium, ERK2, Mitochondria, UPR
Citation
Department
Integrative Biology