dc.creator | Llanes, Joan Manuel | |
dc.date.accessioned | 2020-08-22T17:30:46Z | |
dc.date.available | 2007-07-19 | |
dc.date.issued | 2006-07-19 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-07172006-115717 | |
dc.identifier.uri | http://hdl.handle.net/1803/13100 | |
dc.description.abstract | 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. | |
dc.format.mimetype | application/pdf | |
dc.subject | B cells Differentiation Molecular aspects | |
dc.subject | B cell development | |
dc.subject | B cell receptor signaling | |
dc.subject | Cellular control mechanisms | |
dc.title | Signaling regulation of transitional immature to mature B cell development | |
dc.type | thesis | |
dc.contributor.committeeMember | Dr. Wasif Khan | |
dc.contributor.committeeMember | Dr. Eugene Oltz | |
dc.contributor.committeeMember | Dr. James W. Thomas | |
dc.type.material | text | |
thesis.degree.name | MS | |
thesis.degree.level | thesis | |
thesis.degree.discipline | Microbiology and Immunology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2007-07-19 | |
local.embargo.lift | 2007-07-19 | |
dc.contributor.committeeChair | Dr. Andrew Link | |