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R A Brink

Publications and source records attributed to R A Brink.

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Induction of self-tolerance in mature peripheral B lymphocytes.

In transgenic mice, mature peripheral B lymphocytes in lymphoid follicles, like immature B cells, are rendered tolerant by encounter with self-antigen, provided receptor occupancy by self-antigen exceeds a critical threshold. The tolerant state of the B cell is closely correlated with down-regulation of membrane IgM but not IgD antigen-receptors. Identical changes in antigen-receptor expression occur in a subset of follicular B cells in nontransgenic mice, suggesting that clonally silenced self-reactive cells are common in the peripheral B-cell repertoire.

Animals

Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice.

Immunological tolerance has been demonstrated in double-transgenic mice expressing the genes for a neo-self antigen, hen egg lysozyme, and a high affinity anti-lysozyme antibody. The majority of anti-lysozyme B-cells did not undergo clonal deletion, but were no longer able to secrete anti-lysozyme antibody and displayed markedly reduced levels of surface IgM while continuing to express high levels of surface IgD. These findings indicate that self tolerance may result from mechanisms other than clonal deletion, and are consistent with the hypothesis that IgD may have a unique role in B-cell tolerance.

Animals

Paramutation.

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