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UBC Theses and Dissertations

The effect of the W gene on immune responses in mice McNay, Margaret Lynne


Previous reports that lymphocytes from W/W[sup v] mice migrate more slowly than do lymphocytes from normal mice, and that spleens from W/W[sup v] mice produce fewer plaque-forming cells in response to immunization with sheep red blood cells (SRBC) than do normal mice, suggested that other immune responses in these mice might also be affected. The following experiments have revealed that graft rejection is faster and more vigourous among W/W[sup v] mice than among +/+, normal mice: 1) strongly antigenic, H-2 incompatible, skin allografts examined histologically at the eighth day after transplantation to W/W[sup v] hosts exhibit higher graft rejection scores than do identical skin allografts transplanted to +/+ hosts; 2) weakly antigenic skin allografts bearing the H-Y antigen, when transplanted to female +/+ and W/W[sup v] hosts, are rejected more quickly by W/W[sup v] hosts than by +/+ hosts; 3) the uptake of tritiated thymidine by cells in the peripheral blood of mice bearing skin allografts indicates a greater proportion of activated cells in the circulation of W/W[sup v] mice than of +/+ mice. Confirmation has also been obtained that some antibody responses among W/W[sup v] mice are depressed. In response to immunization with SRBC, W/W[sup v] mice produce about 1/4 the number of plaque-forming cells as do +/+ mice. W/+ and W[sup v ]/+ mice produce intermediate numbers of plaque- forming cells. Titers of SRBC agglutinins produced by W/W[sup v] mice in a secondary response are significantly lower than titers produced by +/+ mice. The uptake of tritiated thymidine by spleen cells stimulated with the B-cell mitogen LPS indicates that W/W[sup v] cells are deficient: in their response to this mitogen. Treatment with the T-cell mitogen Concanavalin-A, however, results in marginally greater thymidine uptake by W/W[sup v] spleen cells than by +/+ cells. These results suggest that T-cell responses generally may be somewhat enhanced and B-cell responses depressed in mice of W/W[sup v] genotype. The altered reactivity of lymphocytes from W/W[sup v] mice can be accounted for by postulating an alteration in the surface characteristics of these cells. The hypothesis that the W locus controls a cell surface characteristic is the only hypothesis yet formulated which is able to account for all the better-known pleiotropic effects of the W mutation (anemia, sterility, and a lack of pigmentation) as well as for its immunological effects. This hypothesis and its implications are discussed in detail in the text.

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