Prevention and treatment of EAE by the induction of clonal anergy to encephalitogenic determinants of myelin basic protein (MBP). Retroviral-mediated gene transfer technology is employed to express synthetic genes encoding the whole myelin basic protein (MBP), proteolipid protein (PLP) or myelin oligodendrocyte glycoprotein (MOG) or minigenes encoding the encephalitogenic determinants of these proteins in normal antigen presenting B cells. These synthetic genes also encode lysosomal targeting sequences in order to facilitate association with MHC class II molecules. The hypothesis is that normal, resting B cells induce antigen-specific T cell unresponsiveness rather than activation. Preliminary results showed that B cells expressing a PLP-derived encephalitogenic determinant completely inhibit the ability to induce EAE in susceptible animals and therefore strongly support this hypothesis.
The developmental pathway of the myeloid system in mice. Using retroviral tagging, a myeloid precursor cell population that can give rise to the whole myeloid system was identified in the spleen. This cell population is non self-renewing, and will not reconstitute the BM of irradiated animals. It is, however, a very long-lived population and will reconstitute the myeloid system for at least six months.
B cell antigen presentation in vivo. The ability of irrelevant, non-antigen-specific B cells to present antigen in vivo is a key question in initiation of immune responses. This question is studied in B cell-deficient (ยต K.O) mice reconstituted with B cells from various Ig transgenic mice followed by local immunizations with antigens different from the specificity of the transgene.