In vivo selection of neutralization-resistant virus variants but no evidence of B cell tolerance in lymphocytic choriomeningitis virus carrier mice expressing a transgenic virus-neutralizing antibody

B cell tolerance is maintained by active deletion and functional anergy of self-reactive B cell; depending on the time, amount, and site of the self-a ntigen expression. To study. B cell tolerance toward a transplacentally tra nsmitted viral Ag, we crossed transgenic mice expressing the mu heavy and t he kappa light chain of the lymphocytic choriomeningitis virus (LCMV) neutr alizing mAb KL2S (HL25-transgenic mice) with persistently infected LCMV car rier mice. Although HL25-transgenic LCMV carrier mice exhibited the same hi gh virus titers as nontransgenic LCMV carrier mice, no evidence for B cell tolerance was found. in contrast, enhanced LCMV-neutraliting;Ab titers acre measured that, however, did not clear the virus, instead, LCMV isolates fr om different tissues turned out to be neutralization resistant Ab escape va riants expressing different substitutions of amino acid ASn(119) of the LCM V-glycoprotein 1 that displays the neutralizing B cell epitope, Virus varia nts with the same mutations were also selected in vitro in the presence of the transgenic mAb KL25 confirming that substitutions of Asn(119) have been selected by LCMV-neutralizing Abs. Thus, despite abundant expression of vi ral neo-self-antigen in HL25-transgenic LCMV carrier mice, transgenic B cel ls expressing LC,LCMV-neutralizing Abs were rather stimulated than tolerize d and neutralization resistant,Ab escape variants acre selected in vivo.