Abstract
THE long-standing hypothesis1,2 that tolerance to self antigens is mediated by either elimination3–8 or functional inactivation (anergy; refs 9-11) of self-reactive lymphocytes is now accepted, but little is known about the factors responsible for initiating one process rather than the other. In the B-cell lineage, tolerant self-reactive cells persist in the peripheral lymphoid organs of transgenic mice expressing lysozyme and anti-lysozyme immunoglobulin genes9, but are eliminated in similar transgenic mice expressing anti-major histocompatibility complex immunoglobulin genes8. By modifying the structure of the lysozyme transgene and the isotype of the anti-lysozyme immunoglobulin genes, we demonstrate here that induction of anergy or deletion is not due to differences in antibody affinity or isotype, but to recognition of monomeric or oligomeric soluble antigen versus highly multivalent membrane-bound antigen. Our findings indicate that the degree of receptor crosslinking can have qualitatively distinct signalling consequences for lymphocyte development.
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Hartley, S., Crosbie, J., Brink, R. et al. Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature 353, 765–769 (1991). https://doi.org/10.1038/353765a0
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DOI: https://doi.org/10.1038/353765a0
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