Are Autoreactive B Cells Deleted?
Understanding the means by which autoreactive lymphocytes are controlled is an essential basis for understanding the mechanisms underlying autoimmunity. Studies of tolerance in the B cell compartment have come to one of three conclusions: (i) B cell tolerance does not exist to a detectible degree (Karray et al, 1986, Rolink et al, 1987); the absence of autoantigen-specific T cell help presumably prevents autoantibody production, (ii) autoreactive B cells are functionally inactivated by interaction with antigen, but persist in the system and are able to bind antigen (Pike et al, 1982, Ventkataraman et al, 1977), (iii) autoreactive B cells are eliminated early in development (Sidman and Unanue, 1975, Metcalf and Klinman, 1977). Recent studies using immunoglobulin transgenic mice expressing light and heavy chain genes encoding antibody specific for certain model autoantigens (Goodnow et al, 1988, Nemazee and Buerki, 1989a) have generated data supporting all of these results, and will hopefully lead to a clearer understanding of the limits to self tolerance.
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