Further studies on supposed lamarckian inheritance of immunological tolerance

Abstract

We have previously reported¹ an unsuccessful attempt to confirm the claim of Gorczynski and Steele^2,3 that tolerance to alloantigens, induced by the inoculation of F₁ hybrid spleen and bone marrow cells in newborn mice, can be transmitted by males to their offspring. Our study had been designed to reproduce the in vitro data of Gorczynski and Steele and to extend them by the transplantation of F₁ hybrid skin allografts. It followed that of Gorczynski and Steele² very closely but differed from it in two respects: the number of semi-allogeneic lymphoid cells in the inoculum used to establish tolerance in the fathers was 5 × 10⁷ instead of 10⁸ and the ratio of spleen cells to bone marrow cells was 9:1 rather than 1:1. Although we argued¹ that it is improbable that these differences of execution could have significantly affected the outcome of the experiments, our departure from the original protocol was nevertheless open to criticism⁴ and the purpose of the present further study was to repeat the experiments by following Gorczynski and Steele² in every respect. We also report an attempt to confirm the work of Guttman's group^5,6, who claimed that a single CBA male made tolerant to A/J histocompatibility antigens, and mated with normal (CBA × A)F₁ females, produced offspring with a higher incidence of hypo- or unresponsiveness to A/J skin or tumour allografts than the offspring derived from normal males. We have again failed to confirm the work of Gorczynski and Steele and, like Steinmuller⁷, we have been equally unsuccessful in confirming the observations of Guttman et al.