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IDENTIFYING A POSSIBLE LINK BETWEEN ECTOPIC GERMINAL CENTERS AND THE EVOLUTION OF TYPE I DIABETES

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The multifaceted phenotype of the B‐lymphocyte has a remarkably effective role in peptide
derived pathogen clearance and the prevention of re‐infection. This mechanism of host tolerant
defense can be attributed to the actions of particular cellular subsets that arise from Blymphocytes:
memory cells and high‐affinity antibody secreting plasma cells. Notably B cell
propagation does not commence without the help of follicular helper T cells (TFH), a specialized
subset of CD4+ cells. TFH cells are involved in the maturation and differentiation of Blymphocytes
after antigen stimulation with a thymus‐dependent peptide. With this specific
stimulus the formation of germinal centers (GCs) within B‐cell follicles of secondary lymphoid
organs is induced and it is within these centers that TFH cells are able to interact with B cells to
facilitate immunoglobulin affinity maturation, somatic hypermutation, and isotype class
switching. Importantly, these respective processes play a fundamental role in manufacturing
high‐affinity antibodies for effective pathogen clearance. Conversely, by means not well
understood, the occurrence of spontaneous GC formation and the mass production of high
affinity autoreactive antibodies have been shown to occur simultaneously with the
development of autoimmune diseases. By the same token this incident is of particular interest
and could play a role in the destruction of pancreatic insulin secreting β cells consequently
driving the pathogenesis of type I diabetes. Our objective is to identify a possible correlation
between the evolution of type I diabetes and the proliferatory behavior of B‐lymphocytes and
TFH cells within developing GCs of non‐obese diabetic (NOD) mouse models.

Identiferoai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/348459
Date04 1900
CreatorsAlcantar, Eduardo C. Jr.
ContributorsThe University of Arizona College of Medicine - Phoenix, Wen, Li MD PhD
PublisherThe University of Arizona.
Source SetsUniversity of Arizona
Languageen_US
Detected LanguageEnglish
TypeThesis
RightsCopyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.

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