Development and follicular localization of tolerant B lymphocytes in lysozyme/anti-lysozyme IgM/IgD transgenic mice.
To analyse mechanisms of immunological self-tolerance, a detailed comparison of the development and fate of lysozyme-specific B lymphocytes was carried out in transgenic mice expressing rearranged anti-lysozyme IgM/IgD Ig transgenes in the absence or presence of an additional transgene encoding lysozyme itself. In the absence of lysozyme, B cell development, localization, and differential expression of transgene-encoded IgM and IgD occurred in the normal sequence in Ig transgenic mice, establishing that these animals provide a physiological model for studies of B cell selection in vivo. By contrast, in lysozyme-expressing double-transgenic mice, tolerant lysozyme-reactive B cells persisted within the follicular mantle zones in the spleen, lymph nodes, and Peyer's patches, but were eliminated from the splenic marginal zones. It could be shown that lysozyme-binding and induction of tolerance occurred as soon as surface Ig was expressed on immature B cells in the bone marrow of the double-transgenic mice although this did not prevent maturation, emigration from the bone marrow, and localization in peripheral lymphoid follicles. These findings, together with recent examples of aborted maturation of self-reactive B cells, indicate two functionally distinct antigen receptor signalling events in immature B cells and suggest a unique role for the follicular microenvironment.
Mason
D Y
DY
Nuffield Department of Pathology, John Radcliffe Hospital, Oxford, UK.
Jones
M
M
Goodnow
C C
CC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression; D007108:Immune Tolerance; D007072:Immunoglobulin D / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology; D013154:Spleen / Q000276:immunology
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D009113:Muramidase