Evidence for a fifth (G) region in theH-2 complex of the mouse

Antisera (B10.129×A)F₁ anti-P and (B10×A)F₁ anti-B10.P contain antibodies that define, in the PVP hemagglutination test, an antigen originally described as G or H-2.7. Of the independentH-2 haplotypes, the H-2.7 antigen is present inf, j, k, p, ands. In addition, the antisera also contain a weak cytotoxic antibody, distinct from anti-H-2.7. The cytotoxic antibody reacts with antigens controlled by theK orI regions. The hemagglutinating H-2.7 antibody does not have cytotoxic activity. The genetic determinant coding for antigen H-2.7 can be mapped into the chromosomal segment between theS andD regions. The H-2.7 antigen thus serves as a marker for a new region of theH-2 complex. The locus coding for antigen H-2.7 is designatedH-2 G and the correspondingH-2 regionG. The H-2.7 antigen has a tissue distribution distinct from that of the H-2 antigens controlled by theK orD regions. So far it could be detected primarily on erythrocytes.     

A new alloantigen,Ly-8, recognized by C3H anti-AKR serum

A new membrane alloantigen, designated Ly-8.2, is defined by a C3H anti-AKR serum. The locus,Ly-8, which controls this determinant is not linked toThy-1, Ly-4, Ly-6, H-2, albino (c), or brown (b). Ly-8.2 has a unique strain distribution, and appears to be present on both T and B lymphocytes.     

Properties of reticulum cell sarcomas in SJL/J mice

While T cells from SJL and from F₁ hybrids of SJL that do not express I-E antigens give strong proliferative responses to RCS, T cells from F₁ hybrids expressing surface I-E do not. The nature of the stimulating antigen on the RCS cell surface was examined using monoclonal antibodies. Complete inhibition of the T-cell proliferative response was obtained with antibodies to I-A antigens, whereas antibodies to I-E antigens did not inhibit at all. This inhibition was mediated via an effect of the antibodies on the stimulating cells. Biochemical characterization of immunoprecipitated ¹²⁵I- and 's S-labeled RCS antigens was performed using two-dimensional gel electrophoresis. Using this technique, I-A antigens were readily detected. However, neither Ia.7-specific antibodies nor antibodies specific for E_α : E _β complexes precipitated any E alpha or E beta chains. Comparison of I-A antigens from RCS and normal SJL spleen cells revealed minor mobility differences in the gels, possibly due to differences in glycosylation, the significance of which needs to be further evaluated. Examination of RNA extracted from RCS, using E alpha and A alpha cDNA probes showed that RCS cells do not transcribe the E alpha gene as has been shown previously for normal H-2 ^s cells. Furthermore, DNA from RCS cells showed a defect in the E alpha gene similar to that known to exist in normal H-2 ^s cells. Our findings exclude the presence of E alpha on RCS cells and suggest a major role for I-A, either alone or in conjunction with another as yet unidentified cell surface antigen, in the stimulation of T cells.     

Further description of theLy-5 system

TheLy-5 system of alloantigens was reevaluated with the aid of an Ly-5 congenic mouse strain and an additional serological technique, the PA-SRBC rosette assay, not previously applied to Ly-5. In the PA-SRBC assay, SRBC to which PA (Staphylococcal Protein A) has been coupled react with antibodycoated cells to form rosettes. The PA-SRBC assay was more sensitive than the cytotoxicity assay in detecting Ly-5 on all cell types tested, with the exception of thymocytes, on which Ly-5 was more efficiently demonstrable by the latter test. Thus, the use of both assays gave a more complete picture of theLy-5 system. Evidently Ly-5 is expressed on most cells of the hematopoietic lineage, but on no other cells so far tested. The Ly-5⁺ cell population includes all known sets of T cells, prothymocytes, sets of B cells, cells of myeloid and monocyte-macrophage types and natural killer cells. Erythrocytes and proerythroblasts are Ly-5^?, but the Ly-5 phenotype of less differentiated erythrocytic cells is uncertain. By means of radiation chimeras, made by restoring lethally irradiated mice with Ly-5 congenic bone marrow, the weakly Ly-5⁺ phenotype of liver and of kidney was shown to be due to immigrant circulating cells. The Ly-5 phenotypes of tumors conform to this scheme of Ly-5 tissue representation. The Ly-5⁺ tumors included more than 40 leukemias tested, plasmacytomas, putative transformed equivalents of slg^?: Lyb-2⁺ early B cells, a mastocytoma, a monocytic line, and three lines related to the macrophage. The other tumors tested -a sarcoma, a spontaneous mammary carcinoma, a teratocarcinoma and a neuroblastoma — were Ly-5^?.     

Probable crossing-over in theB blood group system of chickens

Erythrocytes of two chickens from among 1,206 hybrids obtained from a (CB x CC)F₁xWB cross reacted with antisera against B antigens of all three lines involved in the cross. The possibility that the two birds had not originated from these crosses was excluded. The irregularity observed in cock 744 is accounted for by assuming a recombinant chromosome, B^R1, transmitting part of the B1 and part of the B2 antigenic specificities. Inheritance of B antigens is assumed to be effected by alleles of at least two loci,B-F andB-G. We found that the alleles of theB-F locus determined the serologically defined (SD) and histocompatibility (H) antigens, and the alleles of theB-G locus determined only the SD antigens. The irregularity in theB system of cock 2,349 has not yet been satisfactorily explained.     

Analysis ofH-2 mutants: Evidence for multiple CML target specificities controlled by theH-2K b gene

C57BL/6 (H-2 ^b ) mice and two mutants derived from this strain, B6.C-H-2 ^ba (Hz1) andE6-H-2 ^bd (M505), were studied in a number of functional tests, in vitro and in vivo, that assay for differences at theH-2 complex. All three strains give rise to reciprocal mixed lymphocyte reactivity (MLR) and cell-mediated lympholysis (CML) in vitro as well as graft-host reactivity (GVHR) and skin graft rejection in vivo. Analysis for cross-reactivity between these strains in CML revealed that the gained antigens in each mutant do not cross-react, and that Hz1 has lost an antigen shared by C57BL/6 and M505 strains. In addition, spleen cells from B10.A(4R) mice, which differ from theH-2 ^b haplotype only at theK end of theH-2 complex, recognize a common antigen shared by all three strains tested. Provided that the mutations occurred in theH-2K ^b gene, these data indicate that a) there are at least three antigenic specificities coded for by theH-2K ^b gene(s) that serve as targets for receptors on thymus-derived (T) cells in CML; b) since C57BL/6 strain mice and the mutants are serologically indistinguishable on a qualitative basis, the antigens recognized by the receptors on T cells and by humoral H-2 antibody are nonidentical; and c) mutation in theH-2K ^b locus itself can give rise to allogeneic recognition phenomena such as MLR and GVHR.     

Immune response of mice to the Thy-1.1 antigen: Effect of theIr-5 alleles studied in 129/J and B10.129 (6M) mice

The primary immune response to the Thy-1.1 antigen was measured by a plaque assay that detected cells producing antibodies lytic for AKR thymocytes. B10.129(6M) mice carrying theH-2 complex of an intermediate responder (129) on a low-responder (B10) background, were low responders. Studies employing different F₁ hybrids and segregating generations of 129/J and 6M mice indicated that differences in responsiveness of those two strains depend on alleles at a single locus, loosely linked to theH-2 complex. These results lend further support to the previously advanced concept that the expression of theIr-Thy-1 allcles controlling the response to the Thy-1.1 antigen is influenced by the alleles at theIr-5 locus. In addition, studies employing F₁ hybrids produced through matings of 129/J, 6M, C3H.B10 and C57BL/6J mice to a panel of inbred strains suggested that in regard to the responsiveness to the Thy-1.1 antigen, 129/J and 6M mice are phenotypically, and presumably genotypically, similar to C3H.B10 and C57BL/6J mice, respectively.     

Identification and characterization of the ATP·Mg-dependent protein phosphatase activator (F A) as a microtubule protein kinase in the brain

The activating factor of ATP·Mg-dependent protein phosphatase (F _A) has been identified in brain microtubules. When using purified MAP-2 (microtubule associated protein 2) and tau proteins as substrates,F _A could phosphorylate MAP-2 to 16 moles of phosphates per mole of protein with aK _m value of 0.4 µM, and tau proteins to 4 moles of phosphates per mole of proteins with aK _m value of about 3 µM. When using microtubules as substrates,F _A could enhance many-fold the endogenous phosphorylation of many microtubule-associated proteins including MAP-2, tau proteins, and several low-molecular-weight MAPs. In contrast to other reported MAP kinases, such as cAMP-dependent protein kinase and Ca⁺²/phospholipid-dependent protein kinase, theF _A-catalyzed phosphorylation of tau proteins could cause an electrophoretic mobility shift on sodium dodecyl sulfate polyacrylamide gel electrophoresis, suggesting that a dramatic conformational change of tau proteins was produced byF _A. Peptide mapping analysis of the phosphopeptides derived from SV8 protease digestion revealed thatF _A could phosphorylate MAP-2 and tau proteins on at least four specific sites distinctly different from those phosphorylated by cAMP-dependent and Ca⁺²/phospholipid-dependent MAP kinases. Quantitative analysis further indicated that approximately 19% of the total endogenous kinase activity in brain microtubules was due toF _A. Taken together, the results provide initial evidence that the ATP·Mg-dependent protein phosphatase activating factor (F _A) is a potent and unique MAP kinase, and may represent one of the major factors involved in phosphorylation of brain microtubules.     

Susceptibility to db gene and streptozotocin-induced diabetes in C57BL mice: control by gender-associated,MHC-unlinked traits

H-2 haplotype differences distinguish the related C57BL/KsJ (BKs) and C57BL/6J (B6) inbred strains. BKs mice are more susceptible to diabetes induction by a recessive obesity gene, diabetes (db), or by multi-dose streptozotocin (MSZ) administration. The purpose of this study was to evaluate whether the H-2 differences were the important genetic background modifiers determining inbred strain susceptibility or resistance to these diabetogenic stresses. Diabetes susceptibility of BKs.B6-H-2 ^b congenic mice was compared with that of the parental BKs and B6 stocks. In addition, diabetes severity was studied in (B6 × BKs)F₁ and F₂ db/db mice and an H-2 segregation analysis was performed. BKs susceptibility genes expressed in a dominant fashion in the F₁ generation, and were transmitted to F₂ db/db males without apparent segregation. No association between H-2 ^b haplotype and B6-type diabetes resistance was found in response to either the db mutation or to MSZ. Insulitis, associated with development of hyperglycemia in BKs males, also occurred in the H-2 ^b congenic stock. However, an apparent interaction between H-2 ^b haplotype, the db mutation (on chromosome 4), and male gender (Y chromosome?) was indicated by a segregation ratio distortion in recovery of this genotype. A more moderate diabetes in some F₂ db/db females suggested that non-MHC-linked genes controlling sex steroid metabolism were the important determinants of diabetogenic sensitivities in the C57BL stocks. In support of the latter, strain differences were demonstrated in activity levels of steroid sulfatase, which is regulated by a sex-linked gene likely expressed on both the X and Y chromosome, and which may control tissue levels of active androgens and estrogens. We show that the diabetes-susceptible F₁ hybrids exhibit the higher activity associated with the BKs strain.     

Hybrid immune response to parental liver tissue grafts

Parental-to-F₁-hybrid liver tissue grafts in like-sex donor-recipient combinations survive indefinitely, although several F₁ recipients demonstrate an immunological response to the parental graft. Female F₁ recipients, particularly those carrying theH-2 ^b haplotype, respond vigorously to male parental liver grafts. However F₁ female responses to male parental liver tissue grafts differ substantively from the responses of parental females to syngeneic male grafts. C3H male liver grafts are rejected vigorously by F₁ females as long as the F₁ carries theH-2 ^b haplotype. These findings support previous reports of strong immunological responses to C3H H-Y antigen in female F₁ and C3H.SW animals, a response which is absent in C3H females. Female F₁ hybrids carrying theH-2 ^b haplotype do not reject grafts of B10 or B6 male liver as rapidly as do B10 or B6 parental females. This reduced F₁ response may be related to the formation of hybrid antigens and consequent alteration of the anti-H-Y response. Alternatively, cells that specifically suppress the anti-H-Y response may be present in F₁ hybrids. Factors responsible for suppression appear to be controlled by non-MHC antigens, at least in (OH x B6 or B10) F₁ hybrids.     

Genetics of graft-versus-host reactions (GVHR)

Injection of 20×10⁶ donor lymph node cells (LNCs) into newborn allogeneic recipients incompatible with donors at theIC subregion of the mouseH-2 complex evoked both GVH splenomegaly and GVH mortality. The strength or severity of the allogeneic reactions induced varied as a function of the interallelic strain combination and was influenced particularly by properties of the recipientIC determinants. Thus,IC ^s determinants on recipient cells led to strong GVHR, whileIC ^d determinants induced a moderate GVHR, even when donors carrying differentIC alleles were used. However, responder donor genes also affected the degree of GVHR in some combinations. The effect on donor GVH potential of pre-exposing B10 donors to antirecipient antiserum (B10 anti-B10.A) was also studied. Spleen cells from B10 donors pre-exposed to alloantiserum for two to seven days exhibited a markedly reduced ability to cause GVH splenomegaly and GVH disease in newborn B10. A or (B10. A × B10) F₁ recipients. Inhibition of donor lymphocyte GVH potential waned eight to 14 days after antiserum pretreatment. Inhibition was shown to be specific for variousH-2 determinants and to be caused by antirecipient alloantibodies. Pre-exposure of donors to alloantiserum reduced the GVH potential of spleen cells but did not affect LNC reactivity.Ia antibodies and, to a lesser extent, anti-H-2D serum were shown to be able to inhibit GVHR. The results suggest that the observed reduction in donor GVH reactivity is caused by antibody-mediated central feedback inhibition. Anti-H-2 alloantibodies evidently play an important role in the network regulating allogeneic responses.     

Expression of Ly-6A/E alloantigens in thymocyte and T-lymphocyte subsets: variability related to the Ly-6 a and Ly-6 b haplotypes

We have studied the cellular basis for differential expression of the Ly-6A/E alloantigen on T cells obtained from mice of the Ly-6 ^a (10–20% Ly-6A/E ⁺) and Ly-6 ^b (50–60% Ly-6A/E ⁺) haplotypes. During T-cell ontogeny only a small fraction (< 12 %) of thymocytes expressed Ly-6A/E. By 4 weeks of age adult levels of Ly-6A/E bearing lymphocytes were seen in peripheral lymphoid tissue. Immunohistochemical studies of the thymus revealed that Ly-6A/E⁺ cells were located predominantly in the medulla with small clusters of Ly-6A/E⁺ cells throughout the cortex. Consistent with this result, phenotypic studies showed that in the adult thymus the majority of Ly-6A/E expression was on mature CD4⁺ CD8^– and CD4^– CD8⁺ cortisone-resistant and precursor CD4^– CD8^– thymocytes. However, a much higher percentage of CD4⁺ CD8^– and CD4^– CD8^– thymocytes as well as CD4⁺ CD8^– peripheral T cells expressed Ly-6A/E from Ly-6 ^b mice. Furthermore, although gamma interferon induced increased Ly-6A/E expression in certain thymocyte and T-cell subsets, this induction functioned preferentially for cells obtained from Ly-6 ^b mice. Studies using F₁ hybrid mice (Ly-6 ^a × Ly-6 ^b) indicated that the basal level of Ly-6A/E expression on these subsets appeared to be under codominant genetic control, whereas gamma interferon-induced regulation of Ly-6A/E expression appeared to be under dominant genetic control. Collectively, these results suggest that the expression of Ly-6A/E on a particular T-cell subset is established in the thymus and is a stable characteristic of each haplotype. In addition, the low levels of Ly-6A/E expression for the Ly-6 ^a haplotype appear to be partially due to the inability of the majority of resting CD4⁺ T cells to express Ly-6A/E and to the relatively poor induction of this protein by gamma interferon.     

Cellular immunity in the mouse. IV. Altered thymic-dependent lymphocyte reactivity in the chronic graft vs host reaction and leukemia virus activation.

The lymphocytes obtained from several F₁ strains undergoing chronic GVH reactions were studied for in vitro alterations of thymic-dependent lymphoid function. Spontaneous blastogenesis was increased. The in vitro response to nonspecific mitogenic stimuli (PHA and CON-A) and specific antigenic challenge (SRBC and allogeneic cells) was initially increased and subsequently impaired. The degree of alteration was related to the severity of the observed disease and dependent upon the F₁-parental combination employed. Thymic-dependent lymphocytes obtained from animals with GVH disease possessed the ability to suppress actively the response of normal mouse cells in vitro to various T-cell mitogenic stimuli and this suppressive activity was present in the supernatant culture fluid from such cells. The mechanism of this altered in vitro T-cell reactivity is not yet completely understood, but may in part be related to the immunologic activation of murine leukemia virus from mouse cells undergoing allogeneic stimulation.     

Combined Effects of Lead and Acid Rain on Photosynthesis in Soybean Seedlings

To explore how lead (Pb) and acid rain simultaneously affect plants, the combined effects of Pb and acid rain on the chlorophyll content, chlorophyll fluorescence reaction, Hill reaction rate, and Mg²⁺-ATPase activity in soybean seedlings were investigated. The results indicated that, when soybean seedlings were treated with Pb or acid rain alone, the chlorophyll content, Hill reaction rate, Mg²⁺-ATPase activity, and maximal photochemical efficiency (F _v/F _m) were decreased, while the initial fluorescence (F ₀) and maximum quantum yield (Y) were increased, compared with those of the control. The combined treatment with Pb and acid rain decreased the chlorophyll content, Hill reaction rate, Mg²⁺-ATPase activity, F _v/F _m, and Y and increased F ₀ in soybean seedlings. Under the combined treatment with Pb and acid rain, the two factors showed additive effects on the chlorophyll content in soybean seedlings and exhibited antagonistic effects on the Hill reaction rate. Under the combined treatment with high-concentration Pb and acid rain, the two factors exhibited synergistic effects on the Mg²⁺-ATPase activity, F ₀, F _v/F _m, as well as Y. In summary, the inhibition of the photosynthetic process is an important physiological basis for the simultaneous actions of Pb and acid rain in soybean seedlings.     

Delayed-type hypersensitivity responses to H-Y: Characterization and mapping ofIr genes

This paper examines the delayed-type hypersensitivity (DTH) response to male (H-Y) antigen(s). Female mice of theH?2 ^b haplotype developed delayed footpad reaction to syngeneic or allogenic male thymus and spleen cells after priming with syngeneic male thymus and spleen cells. The reaction peaks at 24 h, has classical DTH histology and is specific to H-Y antigen as it is not elicited with female cells. Cell transfer studies show that donor/recipient matching at theI?B ^b subregion is necessary for sucessful transfer of DTH and that the effective primed population is Thy-1⁺, Lyt-1⁺, 2^?. DTH response to H-Y antigen appears to be confined to mice of theH?2 ^b haplotype. There appears to be a lack of associative recognition between H-Y antigen and MHC-coded determinants in the effector phase of DTH, and macrophage processing of H-Y seems likely, since nonresponder haplotypes can elicit the DTH response. Studies withH?2 ^b recombinant mouse strains indicate that the dominantIr gene is located in theI?B region. Female F₁ hybrid mice derived from matings of strains not involvingH?2 ^b haplotype failed to develop DTH to H-Y. In summary, these data imply that a complete correlation exists between DTH to H-Y and the ability to reject male skin graft, suggesting that the effector mechanisms of skin-graft rejection may closely involve DTH cells.     

Polymorphism of minor histocompatibility genes in wild mice

H-2^b-restricted cytolytic T lymphocytes (CTL) were generated against H-1, H-3, and H-4 antigens and tested against target cells of F₁ hybrids between wild mice and inbred H-2 ^b mice. The congenic strain combinations for the CTL production were such that they tested one allele each at the H-1 and H-4 loci and four alleles at the H-3 locus. Most of the wild mice tested came from Southern Germany, but a few mice came from other European countries and Egypt and Israel. Virtually all wild mice typed as positive with CTL directed against H-3^b and H-4^b antigens; 32% of the F₁ hybrids tested reacted with anti-H-1^cCTL and 9% reacted with anti-H-3^d CTL. The positive results were not caused by cross-reaction with allogeneic H-2 antigens controlled by the major histocompatibility complex (Mhc) genes of the wild mice. At least some of the H-3 and H-4 antigens detected by the CTL in the F₁ hybrid were not identical with antigens of the immunizing strains. These results suggest a relatively low degree of polymorphism of the tested minor H loci in wild mice and further support the notion that minor H loci are unrelated to the Mhc.     

Idiotypic regulation of mouse anti-H-2 antibody responses

Mouse-immunoglobulin (MIg) tolerant rabbits immunized with mouse H-2 antibodies produced anti-idiotype antisera, which were reactive towards specific B- and T-cell receptors. One such rabbit antiserum (from rabbit 5936) defines a family of idiotypes (Id) designated 5936-idiotypes (Rubin et al. 1979). The present experiments were performed in order to establish (1) the nature of 5936-Id⁺ serum molecules, (2) the specificity of 5936-Id⁺ serum molecules, (3) the association of the 5936-Id genes to allotype and/orH-2 genes and (4) the immunological role of 5936-Id⁺ serum molecules. A sensitive, radioimmunoassay employing¹²⁵I-labelled-F(ab)₂ fragments of B6 anti-B10.BR MIg pool, 5936 antiserum, and a sheep anti-rabbit immunoglobulin antiserum, was used.—The results suggested that 5936-Id⁺ serum molecules were exclusively MIg, and that they were mainly of the IgG₁ class. Such molecules were induced in B6 mice (H-2 ^b /Ig-1 ^b ) upon immunization with H-2^k but not with H-2^q alloantigen or conventional antigens. The 5936-Id were found to be associated with Ig-1^b allotypes and theH-2 ^b complex may contain immune response (Ir) genes which, in comparison withIr genes inH-2 ^d andH-2 ^s , favor the expression of 5936-Id.—Adsorption of 5936-Id⁺ B6 anti-CBA MIg preparations on CBA (IA^k) spleen cells demonstrated that CBA antibodies were 5936-Id^?. It is dicussed whether 5936-Id⁺, IgG₁ molecules in B6 anti-CBA sera are anti-(anti-CBA) antibodies or nonspecific antibodies, the production of which is augmented by immunization with IA^k alloantigen.     

Multigenic control of immune responses of inbred mice against the terpolymers poly(Glu57Lys38Ala5) and poly(Glu54Lys36Ala10) and linkage withH-2 haplotype

Results of immunizations of recombinant inbred and congenic strains of mice with the random polymers poly(glu⁵⁷ lys³⁸ala⁵) or GLA⁵ and poly(glu⁵⁴lys³⁶ala¹⁰) or GLA¹⁰ indicate that there is an association of the responsiveness with theH-2 haplotype. Although the C57BL/6J mice (H-2 ^b haplotype) are “non responders”, the C57BL/6By originally derived from mice of the same haplotype are responders. The immune response pattern of recombinant strains carrying haplotypes derived by crossing over within theH-2 complex indicate that the responsiveness is under control of anIr gene which maps to the left of theIB subregion. Studies with the backcross mice indicated multigenic control of the responsiveness, with one locus beingH-2 linked and another locus segregating independently ofH-2.     

Immune responses of mice to poly(L-Tyr-L-Glu-L-Ala-Gly) and its oligomers

C57BL/6 (H-2 ^b) mice, when immunized with the sequential polymer (T-G-A-Gly)_n and its low-molecular-weight oligomers, respond only to theα-helical oligomers with molecular weights of 9700 and above. Only the sameα-helical oligomers were able to inhibit the homologous antigen-antibody reaction. Random copolymers of GA, GT, and GAT¹⁰ did not inhibit. In vitro stimulation of peritoneal exudate lymphocyte (PETLES) cultures showed that the cellular response (T-cell) against (T-G-A-Gly)_n is antigen-specific. In vitro antigen-induced stimulation of whole spleen or lymph node lymphocytes indicated that (T-G-A-Gly)_n might also be a B-cell mitogen.     

Tests of association of immunoglobulin allotype genes and viral oncogenesis in chickens

Chickens from Regional Poultry Research Laboratory (RPRL) inbred line 6₃ are resistant to virally-induced Marek's disease (MD) and lymphoid leukosis (LL) and are relatively strong regressors of virally-induced Rous sarcomas. In contrast, RPRL line 100 chickens are highly susceptible to MD and LL and are weaker regressors of Rous sarcomas than line 6₃. RPRL lines 100 and 6₃ differ for alleles at the IgG-1 (G-1) allotype locus, but have identical IgM-1 (M-1) allotype alleles. To test the possible association of the G-1 locus with variations in resistance to virally-induced tumors, homozygous and heterozygous genotypes among F₃ crosses were infected. F₃ chickens with different G-1 types were comparable in their resistance to MD tumors following inoculation with the JM strain of the MD virus, and for their ability to regress Rous sarcoma tumors induced by the Rous sarcoma virus (RSV) RAV-1. However, following RAV-1 virus infection a smaller proportion of G-1 ^a /G-1 ^a F₃ or F₄ birds developed LL tumors than G-1 ^a /G-1 ^e and G-1 ^e /G-1 ^e birds. Genes determining immunoglobulin heavy chains were therefore associated with a recessive resistance to B-cell lymphomagenesis in chickens.Deceased