Although studies using B cell deficient mice have been useful in understanding the importance of B cells under different conditions, it is difficult to then dissect exactly how B cells could be regulating T cell responses. By transferring OT-II transgenic T cells into either B cell deficient (μMT) or C57BL/6 mice, expansion and contraction of T cells can be tracked <i>ex vivo. </i>Expansion of OT-II cells is reduced in μMT mice compared to C57BL/6 mice. Thus, B cells can provide costimulatory signals, secrete cytokines and influence the lymphoid microarchitecture. To dissect which B cell factor(s) are involved in enhancing OT-II T cell expansion, a model system was used where one molecule on the B cells is depleted at one time. This was achieved by creating bone-marrow chimeras using a combination of μMT bone-marrow and wildtype or deficient bone-marrow. Thus, all the B cells are either wildtype or deficient for a particular molecule. The molecules examined were MHC-II, which is required for antigen presentation, CD40, due to its costimulatory role, and lymphotoxin-alpha, for its role in maintenance of splenic architecture. Using the OT-II adoptive transfer system, we have shown a requirement for MHC-II but not CD40 on B cells for efficient T cell expansion. In light of these observations, the role of B cell-derived MHC-II for T cell memory generation was examined. To do this, I used MHC-II tetramers to track a polyclonal population of T cells in the host. Using this technique, I have shown that T cell memory is also diminished when the B cells do not express MHC-II. Thus, a cognate interaction with B cells is required for both efficient expansion and memory generation of CD4<sup>+</sup> T cells.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:645118 |
| Date | January 2005 |
| Creators | Crawford, A. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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