Advisory Committee Chair
Louis B Justement
Advisory Committee Members
David Chaplin
Christopher Klug
Chander Raman
Casey Weaver
Document Type
Dissertation
Date of Award
2007
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
The evolution of multicellular organisms necessitated the ability to detect and remove harmful parasitic microorganisms from the host. This simple requirement for self non-self discrimination has evolved in vertebrates into an elaborate system consisting of a variety of effector mechanisms to perform this process. The immune system is often described as consisting of two distinct yet complimentary components, the innate and adaptive immune systems. It is now recognized that the immune system relies on the highly coordinated interplay between a variety of cell types which cooperate to maintain the health of the organism. The work outlined in this dissertation addresses this interplay between the adaptive and innate immune systems in two ways. First is the characterization of TLT2, a cell surface receptor expressed on B lymphocytes, macrophages, and granulocytes. In macrophages and granulocytes the expression of TLT2 is upregulated in response to inflammatory stimuli. Within the B cell compartment expression of TLT2 is highest on “innate like“ peritoneal B1 and marginal zone B cells, which are responsible for the rapid humoral response to Thymus-Independent (TI) antigens. The second manuscript presented in this thesis addresses the function of Hematopoietic SH2 containing adaptor protein (HSH2) in B lymphocytes. Previous reports suggested that HSH2 functions as an anti-apototic protein. To directly test this hypothosis in vivo mice were generated that constitutively express HSH2 in B lineage cells as a transiv gene. Despite a resistance to antigen receptor induced apoptisis in vitro, these mice exhibit a delay in population of the peripheral B cell compartment, contain lower levels serum Igs, and produce an attenuated humoral response to both T-dependant (TD) and Tindependent (TI) antigens. These effects appear to be the result of a decreased responsiveness of B lymphocytes from HSH2 Tg mice to stimulation through the TNF receptors CD40 and BAFF-R. These results suggest that exposure to activating stimuli including toll ligands may fundamentally affect the subsequent response of B cells to the costimulatory molecules CD40L and BAFF by promoting the expression of HSH2. Thus this study provides another mechanism by which exposure to “innate” stimuli (toll ligands) directly affect the subsequent adaptive immune response.
Recommended Citation
King, R Glenn, "On The Immunological Roles Of Tlt2 And Hsh2" (2007). All ETDs from UAB. 3732.
https://digitalcommons.library.uab.edu/etd-collection/3732