Self versus non-self carrier in primary and secondary anti-TNP B cell response: I. Specificity of help.

Humoral anti-hapten responses are supposed to require carrier-specific help. Yet, "TNP-specific" help can be activated with TNP coupled to syngeneic lymphocytes. To further clarify the role of hapten-specific vs. carrier-specific helper T cells (TH) in the humoral anti-TNP response, BALB/c mice were immunized with TNP coupled to cellular or soluble self or non-self carriers, and we analyzed primary and secondary B cell responses as well as the apparent specificity of help. TNP bound to syngeneic red blood cells (sRBC), syngeneic albumin (sA) and syngeneic polyclonal or monoclonal immunoglobulin (sIg/smIg) and TNP coupled to non-self carriers initiated equivalent primary anti-TNP responses. On the other hand, a secondary anti-TNP response was only obtained with heterologous carriers or with smIg. Even with heterologous carriers or with smIg, the magnitude of the secondary anti-TNP response exceeded only slightly the amplitudes of a primary anti-TNP response. Furthermore, if animals were challenged shortly after priming, they appeared un/-hyporesponsive. In vitro analysis revealed that in the primary as well as in the secondary anti-hapten response, TNP-specific TH were involved, i.e., the primary response to sIg, sA and sRBC was exclusively due to TNP-specific help, the response after priming with TNP-smIg or TNP-heterologous carrier was due to the additive effects of carrier- and TNP-specific help. Since "carrier-specific" help with smIg was independent of the antibody specificity as well as of the Ig class, we suppose that smIg activated idiotype-specific TH, which functioned like "carrier" TH. Two mechanisms were responsible for the low magnitude of the secondary anti-hapten response: competition for carrier-specific help (using heterologous carriers), and antibody (AB)-dependent suppression.