Carrier-priming leads to hapten-specific suppression

Studies over the past two decades have established1,2 that ‘helper’ T lymphocytes primed to a ‘carrier’ protein increase B-lymphocyte antibody responses to ‘haptenic’ determinants on the carrier protein. T cells from donors primed with one commonly used carrier protein, keyhole limpet haemocyanin (KLH), have been shown by many workers to augment B-cell IgG anti-dinitrophenyl (DNP) responses in adoptive recipients stimulated with DNP-KLH. Therefore, we were surprised recently to find that the KLH-primed mice we normally use as donors for carrier-specific helper T cells in adoptive transfers3 show reduced rather than augmented IgG in situ anti-DNP antibody production when stimulated with DNP-KLH. Here we show that hapten-specific regulation of antibody production is responsible for this response failure. That is, that KLH-priming before DNP-KLH exposure reduces the production of IgG anti-DNP antibody without interfering with the anti-KLH response or with the development of anti-DNP memory B cells, and that IgG anti-DNP production remains low after further stimulation with DNP on KLH or an unrelated carrier. Thus initial stimulation with a carrier-protein creates an oddly compromised animal in which IgG antibody production to a ‘new’ haptenic determinant on the carrier is kept minimal despite the presence of normal anti-hapten memory and carrier-specific help capable of supporting other responses to the hapten-carrier conjugate.