Year: 2000
Type: dissertation
Abstract: The proliferation, survival and differentiation of B cell precursors depends on extracellular signals provided by cells within the microenvironment. Cell-bound and secreted molecules direct B lineage progression and regulate the selection of clones from which the immune repertoire emerges. In fact, a myriad of signals derived from B cell progenitors themselves and the microenvironment, in which they develop, cooperatively regulate the progression of progenitors along the B lineage pathway. In this thesis, I describe several new molecular interactions that had previously not been considered to play a role in the early B cell differentiation process. I first characterize the cloning of a gene encoding a sialic acid specific 9-O-acetylesterase that was isolated by differential display analysis of a preBCR- proB cell line and a preBCR+ preB cell line. Differential expression is confirmed by the analysis of several B cell lines and primary B lineage cells. Furthermore, the isolation of various cDNA clones with differing 5 ' sequences suggests an additional level of transcriptional regulation. This finding directs my studies to an examination of the B lineage-specific, sialic acid-binding lectin CD22, whose interactions are modified by 9-O-acetylation. In contrast to previous reports, I show that surface CD22 is expressed at an early stage of development. The study of CD22, whose ligands are also expressed at an early stage of development, finally leads to an analysis of the role of homotypic B cell precursor interactions during B cell development. Using an 'in vitro' assay system I demonstrate that interactions between B cell precursors themselves promote their further development to a mature B cell stage. That preB-preB interactions promote or regulate the critical preBCR-driven signal is suggested by the dramatic inhibition of maturation observed upon blocking [mu] heavy chain cell surface interactions. In summary, these results suggest two novel means of regulating the B cell differentiation process: the regulation of early CD22 interactions through 9-O-acetylation and the generation of differentiation signals through homotypic B cell precursor interactions.
Author: Angela Stoddart
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: National Cancer Institute
OpenAlex ID: W2728106811