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Title page for ETD etd-09182006-172759


Type of Document Dissertation
Author Woodward, Emily Jean
Author's Email Address emily.woodward@vanderbilt.edu
URN etd-09182006-172759
Title Autoreactive B cell development in the periphery
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Wasif N. Khan Committee Chair
Eugene M. Oltz Committee Member
James W. Thomas Committee Member
Mark R. Boothby Committee Member
P. Anthony Weil Committee Member
Keywords
  • autoimmunity
  • diabetes
  • immunoglobulin
  • zinc finger protein
  • marginal zone
  • B cell
  • autoreactive
  • Notch2
Date of Defense 2006-09-15
Availability unrestricted
Abstract
Self-reactive B lymphocytes are frequently produced as a consequence of B cell antigen receptor rearrangement. Autoreactive B cells that are not eliminated or inactivated by tolerance mechanisms survive and mature in the periphery. In the spleen, the marginal zone serves as a reservoir for autoreactive B lymphocytes. Marginal zone B cells are known for their rapid and robust responses to T-independent stimuli and serve functions in both the innate and adaptive arms of the immune system. Anti-insulin transgenic B cells are preferentially selected into the marginal zone and are functionally anergic. These cells provide an opportunity to study how autoreactive B cells mature into the marginal zone subset. Using the anti-insulin transgenic model, we find that multiple factors influence marginal zone B cell maturation. These elements include B cell receptor specificity, lineage regulators such as Notch2, and a differentially expressed transcriptional profile. Understanding the processes that regulate marginal zone B cell maturation and how anergy is maintained in this population will impact our ability to manage these cells in host defense and autoimmune disease.
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