W. R. Dunlop

TheB locus (MHC) in the chicken: Association with the fate of RSV-induced tumors

The fate of tumors induced by Rous sarcoma virus (RSV) was determined in anF2 population segregating at three alloantigen loci. TheF1 resulted from crossing tumor-resistant RPRL line 61 (B2B2D3D3I2I2) with tumor-susceptible RPRL line 151 (B5B5D4D4I8I8). Among theF2 segregantsB2B2,B2B5, andB5B5, the percentage of chicks dying of terminal tumors (by 70 days post-inoculation) was 5, 26, and 93, respectively (P≦0.01). NeitherD orI genotypes nor sex significantly affected tumor growth. In chickens with terminal tumors, the incidence of metastatic lesions was also significantly associated withB genotypes. Thus, the MHC chromosomal region in the chicken appears to exert a crucial role in determining the outcome of RSV-induced tumors.

B locus (MHC) effect upon regression of RSV-induced tumors in noninbred chickens

The incidence of regression of Rous sarcoma virus (RSV)-induced tumors in a noninbred line of New Hampshire chickens was approximately six percent (Cotter et al. 1973, Collins et al. unpublished data). But in a mating of one sire with two dams from this line, the mean incidence of tumor regression (of 30 progeny developing tumors) was 50 percent (Collins et al. unpublished data). Thus, although essentially a progressor line, certain individuals transmitted genes favorable to tumor regression. More recently Collins and co-workers (1977) studied the fate of RSVinduced tumors in an F 2 population from a cross of RPRL inbred lines 61 and 151 which was segregating at three alloantigen loci(B, D and I). Among the F 2 segregants B:B 2, B:B 5, and BSB 5 the percentage of chickens dying of terminal tumors by 70 days post inoculation was 5, 26 and 93, respectively. Seventy-five percent of B:B 2 chickens completely or partially regressed their tumors in contrast to none of the BSB 5 animals. The D and I loci had no detectable effect on tumor regression. Schiermann and co-workers (1977) concluded that regression of RSV-induced tumors was a dominantly inherited trait controlled by a gene within, or closely linked to, the major histocompatibility complex (MHC). Thus, in the chicken the MHC, for which the B blood group system serves as a marker, has a gene(s) which dramatically affects the fate of RSV-induced tumors. The objective of this research was to determine the effect of genes in the immediate chromosomal region of the MHC on tumor regression in this line of New Hampshires. Chickens were produced in two hatches from a flock mating of a noninbred line of New Hampshires, U N H 105, known to be genetically susceptible to subgroup A RSV. Chicks were blood typed for B alloantigens at 4 weeks of age using reagents developed in stocks originating from inter se matings of crosses between White Leghorns and experimental birds of heavy breed origin. Three alleles, B 23, B 24 and B 26 had been previously established as existing in this line (Brilles, unpublished). Using appropriate reagents, the 131 chicks from the two hatches were classified into six genotypes-B23B 23, B24B 24, B26B 26, B23B24, B2SB 26, and B24B26. A highly purified pseudotype of Bryan high-titer Rous sarcoma virus designated BH RSV(RAV-1),

MHC and Non-MHC genetic influences on rous sarcoma metastasis in chickens

The B5/B5 genotype, in Leghorns, was associated with a high degree of metastasis of Rous sarcoma virus-induced tumors, but in combination with a Leghorn-New Hampshire background markedly less metastasis occurred. Initially, four mating types were used: B5/B5 × B5/B5 chickens from the F5 generation of the cross of Leghorn lines 61 and 151, B24/B24 × B24/B24 chickens from line UNH 105 (New Hampshires), and reciprocal crosses of B5/B5 × B24/B24 chickens. Subsequently, F2 generation progeny of the cross of B5/B5 and B24/B24 breeders, as well as B24/B24 line UNH 105 and B5/B5 (61 × 151)F2 chickens, were used. Six-week-old chickens were inoculated in the wingweb with Rous sarcoma virus. Chickens dying during a 10-week period after inoculation were necropsied and suspect metastatic lesions examined histologically. Among 234 terminal chickens from the initial four mating types the incidence of metastasis associated with B5/B5 Leghorns (66%) was substantially higher than for B24/B24 New Hampshires (12%) and B5/B24 progeny of reciprocal Leghorn-New Hampshire crosses (19 and 24%). Subsequently, among 524 terminal hosts in the Leghorn-New Hampshire F2 population, B genotype significantly influenced tumor dissemination. However, among 52 concurrently challenged B5/B5 hosts from the (61 × 151)F2 population the incidence of metastasis (60%) was significantly higher than among 122 B5/B5 hosts from the Leghorn-New Hampshire F2 population (31%), indicating a non-major histocompatibility complex genetic effect on metastasis.