R. W. Briles

Identification of haplotypes of the chicken major histocompatibility complex (B)

The chromosomal region presently known to contain the major histocompatibility complex of the chicken was first detected in 1947 using alloimmune hemagglutinating reagents and was tentatively assigned the locus symbol D in studies on the time of development of cellular antigens (Briles et al. 1948) and on its role in inducing hemolytic disease among chicks from alloimmunized hens (Briles 1948). The locus symbol was subsequently changed to B to symbolize the second chicken blood group system discovered at the University of Wisconsin (Briles et al. 1950). One of two blood group loci discovered independently by Gilmour (1959) was shown by an exchange of antisera to correspond to the Wisconsin B system. The early recognition that blood group systems were characterized by extensive polymorphism within rather narrowly based genetic stocks of chickens (Briles et al. 1957, Gilmour 1959) placed emphasis on investigating their possible effects on fitness and survival within populations or experimental crosses. As a result of this emphasis on within-laboratory studies, there was little sustained interest during the 1950-1970 period in the development of a broadly applicable system of uniform haplotype terminology. The discovery of histocompatibility-linked immune response genes in mammals (Benacerraf and McDevitt 1972) and the subsequent demonstration of immune response (Giinther et al. 1974, Benedict et al. 1975) and disease resistance (Hansen et al. 1967, Briles and Oleson 1971) associated with particular alleles at the B locus in the chicken created a need for information regarding possible haplotype homologies between genetic stocks being studied in separate laboratories. The technique for detecting possible homologies between lines was utilized from the beginning of the work at Texas A and M University (Briles 1952, Briles et al. 1957) and, soon after establishing work on a diverse group of mildly inbred lines at the DeKalb AgResearch Laboratory in early 1958, a common haplotype terminology across lines was developed and later published in part to illustrate frequency profiles in inbred parent lines of chickens (Briles 1972). More recently, as a consequence of reagent preparation in a genetically diverse chicken colony at Northern Illinois University combined with the typing of

Some Recent Recombinants at the B Locus

The multi-locus nature of the major histocompatibility complex in the mouse and in man has been well established (1, 2). The association of the major histocompatibility complex of the chicken with immune response to specific antigens (3), complement activity (4), and susceptibility to Marek’s Disease (5,6), has heightened interest in the genetic nature of the B chromosomal region of this species. From functional and evolutionary standpoints, it would be informative to learn to what extent such multi-locus complexity also characterizes the major histocompatibility system in this phylogenetically more primitive species.

Cellular expression of MHC glycoproteins on erythrocytes from normal and aneuploid chickens.

The major histocompatibility complex (MHC) in the chicken (B-complex) encodes glycoproteins homologous in function and distribution to the mammalian MHC. These are the B-F (class I) and B-L (class II) glycoproteins. In addition, a third glycoprotein (B-G) is also encoded by the chicken MHC. We are interested in examining gene regulation and cellular expression of these MHC gene products in the chicken. The trisomic line of chickens is being developed as an animal model for this purpose. Birds from this line contain either 2, 3, or 4 MHC-encoding chromosomes. In this study, we investigated the hypothesis that the quantities of B-complex glycoproteins on the membranes of fully differentiated erythrocytes are proportional to the number of MHC-encoding chromosomes present in particular birds. Hemagglutination final titer and quantitative adsorption assays were carried out using erythrocytes from disomic and aneuploid chickens homozygous for the B15 haplotype. The average hemagglutination final titers were higher for tetrasomic cells as compared to disomic cells. Furthermore, in adsorption assays, employing a B15 cross-reacting alloantiserum, trisomic and tetrasomic erythrocytes displayed increased adsorption capabilities (1.6 and 3.1 fold, respectively) compared to disomic control cells. These results indicate a step-wise increase in the amounts of erythrocyte surface glycoproteins per cell in the trisomics and tetrasomics, respectively. Such findings are consistent with a MHC-dosage-dependent model of gene expression in homeothermic vertebrates.

Inflammatory function of macrophages from chickens with B‐recombinant haplotypes

Both in vivo macrophage activation and in vitro monocyte activation were compared using chickens homozygous for each of two biochemically and serologically similar B-complex recombinant (B(F2-G23)) haplotypes. Chickens carrying the parental (non-recombinant) B haplotypes (B2 and B23) were included for relative comparison, although the genetic backgrounds for these strains were different from the background of the recombinants. Elicited peritoneal macrophages from R4/R4 (international designation B(2r3)) chickens expressed levels of sheep erythrocyte phagocytosis which were significantly higher (P< 0.05) than those from R2/R2 (B(2rl)) chickens. Differences between chickens with B genotypes were analogous to the differences demonstrated previously between B2/B2 and B23/B23 chickens. Similarly, lipopolysaccharide (LPS)-activated monocytes from R4/R4 chickens also expressed significantly higher (P< 0.05) levels of phagocytosis when compared with R2/R2 and B23/B23. In both cases, the functional level of macrophages from R2/R2 chickens was similar to that of B23/B23 cells, whereas macrophages from R4/R4 chickens were similar in functional capacity to those from B2/B2 chickens. These results suggest that R2 and R4 recombinants, despite their demonstrated similarities, may differ in DNA regions which include genetic factors controlling macrophage responsiveness.