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Studies of murine B cell differentiation affected by interleukins produced by T-helper cells using clonal models

Posted on:1999-01-23Degree:Ph.DType:Dissertation
University:Michigan State UniversityCandidate:Takayasu, HirokoFull Text:PDF
GTID:1464390014968393Subject:Health Sciences
Abstract/Summary:
The differentiation processes of B cells are influenced by T helper (Th) cells in the immune system, and this interaction is mediated in part by soluble factors such as Interleukins (ILs), multi-functional peptide hormones produced by T cells. Studies using inducible clonal B cell lines were carried out in order to elucidate the underlying mechanisms of the late acting factors from T cells, which are required for B cells to mature into IgM secreting plasma cells. The combined use of inducible clonal cells and recombinant ILs reduced the complexity of the cellular environment for interaction. Differentiation was assayed both at the level of the secretion of the assembled antibody molecules (IgM polymer) and transcription of antibody subunits gene (us and J).;The second T cell factor which induces IgM secretion by a murine B cell-type clone BCL1-3B3, previously shown to react to IL-2, was identified to be IL-5 in the current study. A mixture of IL-2/IL-5 and, to a lesser extent, IL-2 or IL-5 by themselves induced IgM secretion. Each factor can increase mu s and J chain mRNA. Thus, the BCL1-3B3 cells can be stimulated to secrete IgM by a Th-1 factor, interleukin 2 (IL-2), and/or by a Th-2 derived factor, interleukin 5 (IL-5). In addition, these interleukins act together to stimulate IgM secretion to a greater extent than can be induced by either interleukin alone. The IL-2 and IL-5, thus appear to be functionally equivalent relative to their effect on BCL1-3B3 cell differentiation. The cell-cycle analysis experiments suggest, however, IL-2 and IL-5 appear to differ in their cell cycle dependency for signal transmission. The similarities and differences in the response of the cells to two different ILs may help to elucidate the underlying molecular mechanisms in B cell differentiation. A similar study on another cell line AKR-225 cells has been started, and the preliminary data suggest that the cell line responds to Th-2 factors, IL-4 and IL-5.
Keywords/Search Tags:Cells, Differentiation, IL-5, IL-2, Clonal, Interleukin, Factor
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