Characterization of B Cell Development and Activation in the Absence of Akt or Presenilin

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Doctor of Philosophy (PhD)
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Immunology
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Akt
Presenilin
Notch
B cell
Immunology and Infectious Disease
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Abstract

The biochemical pathways critical to B cell development remain poorly defined. Here I characterize a critical role for two separate families of proteins, Akt and Presenilin in the development and activation of B cells. The absence of Akt1 and Akt2 leads to a block in marginal zone (MZ) and B1B cell development, as well as decreased cellularity of splenic follicular B cells. In addition, I find the combined loss of Akt1 and Akt2 causes altered B cell receptor repertoire and poor competitive ability when matched against wild-type B cells. Similar to deficiencies in the Akt pathway the combined loss of Presenilin1 and Presenilin2 results in defective MZ, B1B cell development, and altered BCR repertoire selection. Furthermore, I find that these defects are independent of the Notch pathway and that Presenilins are required for optimal responses to cross-linking of the BCR. Collectively, these findings identify and phenotypically characterize two novel pathways important to B cell development and function.

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David Allman, Ph.D.
Date of degree
2010-05-17
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