Assignment 2 - A Human Bone Marrow Chimera
The T cell progenitors generated from the transplanted bone marrow migrate to the thymus. Firstly, they will go through the positive selection with the help of thymus cortical endothelial cells, learning to recognize the MHC molecules on the "self" cells. Then the remaining T cells experience the negative selection, where those bind to MHC too strongly and start response will be eliminated. The negative selection process is dependent on the bone marrow-derived cells (macrophages, etc.). One of the differences between T and B cell development is that B cell development happens in the bone marrow. In conducting the bone marrow transplants, it is important to match MHC haplotypes. Through the molecular mimicry or alternative recognition, the host T cells may recognize and bind with the donor's MHC molecules, but the side chains bound are different. Since the T cell never see this complex before, they identify the cell as "non-self" and induce the rejection response.
After the successful bone marrow transplantation, the MHC molecules on cells derived from the donor bone marrow will match the haplotype expressed on the donor's kidney. Therefore, the patient will be able to accept the kidney transplantation from the same donor.
After the migration of naÃÂ¯ve T cells into the lymph node, they still have a limited functionality. In normal conditions, the dendritic cells keep moving back and forth between tissues and lymph node, presenting "self" peptides to the naÃÂ¯ve T cells. Since there is no co-stimulatory ligands expressed on the dendritic cells, the only binding force is between the MHC molecules on the dendritic cells and the CD4+ T cells, which is too weak to trigger the T cell differentiation. The T cells will have a weak proliferation and then be eliminated. However, when the dendritic...