Alterations of idiotypic profiles: the cellular basis of T15 dominance in BALB/c mice.

Phosphorylcholine (PC) is a component of cell walls and membranes from a variety of widely distributed microorganisms. It is highly immunogenic in mice and most murine strains have circulating anti-PC antibodies which are known to confer protection against certain bacterial infections. BALB/c mice offer a striking example of a high responsiveness to PC, a propensity to generate PC-binding myelomas, and a great restriction of idiotype expression in anti-PC antibodies; in fact, most BALB/c anti-PC IgM antibodies express the T15 idiotype marker. Although it has been suspected that T15 dominance is somewhat related to the continuous antigenic load presented by microorganismal flora found in conventional mice, a complete experimental account of how antigenic selection brings about such extreme idiotypic dominance is not yet available. In the studies presented below, we investigated the role played by the host environment, T cells, and antigen in affecting the generation of the anti-PC T15 idiotype profile in lethally irradiated adoptive hosts reconstituted with syngeneic neonatal liver cells. The results presented herein indicate that the transfer of mature carrier-primed T cells with neonatal liver cells does not influence the generation of the T15 idiotype profile. We also demonstrated that anti-T15 idiotype suppressed mice, used as lethally irradiated hosts of immature immunocompetent cells, allow an increased rate of reconstitution of the anti-PC response when compared to nonsuppressed hosts. Since the administration of a T15+ anti-PC antibody inhibits both reconstitution and idiotype expansion, we conclude that T15+ B cells do not self-promote themselves. In contrast, we observed that exposure of adoptive hosts to PC antigens can enhance the anti-PC response and alter the idiotypic profile in favor of T15-bearing clones. The failure of T15 idiotype and the success of PC antigens in promoting T15 dominance led us to search for an "antigen inside" which might play a role in the ontogeny of T15 expression. To this end, we produced isologous anti-T15 hybridomas and selected one BH8 binding IgM hybridoma, 15B1, as a potential carrier of an internal image of PC. In vivo tests involving the administration of this antibody to irradiated adoptive hosts immediately prior to the transfer of neonatal liver cells indicate that T15 expression in adoptive transfer can be enhanced by this antibody. Finally, we discuss a model to account for the generation of T15 dominance in normal adult BALB/c mice and its loss in adult BALB/c mice used as adoptive hosts for syngeneic immature immunocompetent cells.(ABSTRACT TRUNCATED AT 400 WORDS)