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Title page for ETD etd-07172006-115717

Type of Document Master's Thesis
Author Llanes, Joan Manuel
URN etd-07172006-115717
Title Signaling regulation of transitional immature to mature B cell development
Degree Master of Science
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Dr. Andrew Link Committee Chair
Dr. Eugene Oltz Committee Member
Dr. James W. Thomas Committee Member
Dr. Wasif Khan Committee Member
  • B cells Differentiation Molecular aspects
  • B cell development
  • B cell receptor signaling
  • Cellular control mechanisms
Date of Defense 2006-07-14
Availability unrestricted
The immature B cell compartment in the spleen comprises of two subsets termed Transitional Type 1 (T1) and Transitional Type 2 (T2). Our laboratory has shown that T1 and T2 B cell subsets respond differently to crosslinking of the BCR; T1 cells die upon BCR stimulation whereas T2 cells proliferate and differentiate into a mature B cell phenotype. The signaling mechanisms that control these disparate biological outcomes in T1 versus T2 cells remain elusive. I hypothesize that the composition of the BCR signalosome is altered during T1 to T2 B cell development. This in turn activates distinct signaling pathways in response to BCR crosslinking. I performed cDNA microarrays and proteomic approaches to define the global genetic and biochemical signaling programs that control the differential BCR responses of T1, T2 and mature B cells. Through proteomics I identified the serine/threonine phosphatase PP2A, CD45 associated protein (CD45-AP) and a never before identified protein in B cells, Src Kinase Associated Phosphoprotein (SKAP55) specifically in T1 but not T2 or mature B cells. Through microarray analysis we found that pro-apoptotic genes did not show any significant difference among T1, T2 and mature B cells, but T1 cells did have lower levels of two anti-apoptotic genes, A1 and Bcl-2. This suggests that the effect in B cell survival of T1 cells may be due to lower expression of anti-apoptotic genes. In addition I found that T1 B cells had lower levels of NF-kappaB1 and NF-kappaB2. Thus, global genomics and proteomics are feasible approaches to help define the unique characteristics of the transitional B cell subsets that underlie their differentiation.
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