B cell tolerance induced by polymeric antigens. I. Comparison of thedose and epitope density requirement for inactivation of primed and unprimed B cells in vivo

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Abstract
Hapten [2,4-dinitrophenyl (DNP)]-specific tolerance was induced in nonimmun or DNP-hemocyanin (DNP-KLH) primed mice by administering hapten-conjugated type 3 pneumococcal polysaccharide (DNP-lys-S3). The dose of DNP-lys2.5−S3 required to suppress the primary anti-DNP antibody responses was appaprox-imately ten times higher than that required to suppress the secondary response Large doses of lightly substituted antigen (DNP-lys0.6−S3) had no effect on prim-ary antibody responses, while small doses of this conjugate suppressed 90—95 % of the secondary response. The conclusion from this (presumably B cell) tolerance model is that B lymphocytes “mature” in their susceptibility to tolerization following primary contact with immunogen, since primed cells are inactivated by lower doses of tolerogen, and by tolerogen with lower epitope density, than no immune B cells. These and other data suggest that the tolerance threshold of B lymphocytes is related to their state of differentiation, and especially to their antigen-binding characteristics.