Simultaneous yet independent inheritance of somatically acquired tolerance to two distinct H-2 antigenic haplotype determinants in mice.

We have previously presented evidence that somatically acquired immunological tolerance to foreign histocompatibility antigens induced in male inbred mice can be transmitted at a high frequency to first- and second-generation offspring without exposure of the progeny to the tolerizing antigenic stimulus. These data have in turn been interpreted to support a hypothesis predicting soma to germ-line inheritance for acquired states of the immune system. Formal proof of this genetic scheme at the molecular level is not yet available. However, an even stronger reason for abandoning the notion of the isolation of the germ line from the soma (Weismann's doctrine) would be provided by a clear demonstration of the multiple inheritance of independently acquired somatic characters. Here we present evidence that individual male mice (B10) made tolerant to two different H-2 haplotypes (B10.BR, B10.D2) can transmit the tolerance state to each haplotype independently, yet often simultaneously, at a high frequency to both first and second generation progeny.