Types Of Chimeras Research Articles

Genetic constitution of germ cells in intervarietal and interspecific chimeras of Brassica induced by in-vitro grafting

The characteristics of intervarietal and interspecific chimeras synthesized by the graft-culture method were determined by morphology, anthocyanin pigmentation pattern, and crossing. In an intervarietal chimera between 'YR-ranpou' (green cabbage) and 'Ruby ball' (red cabbage) in Brassica oleracea, a segregation phenomenon was noted in which seeds giving rise to purple and green plants were both produced in a single capsule in F1 progeny from crosses of chimeras with YR ranpou, the anthocyanin-free graft partner type. The degrees of segregation varied, reflecting the structure of the chimeras. YR ranpou-dominant chimeras produced capsules in which seeds gave rise to green plants at a high frequency, while Ruby ball-dominant chimeras produced capsules in which seeds in one capsule gave rise to purple plants at a high frequency. Mixed chimeras produced capsules with green plants or purple plants more regularly than did other chimeral types. Furthermore, a chimeral type in which seeds gave rise to green and purple plants was found in 3.2% of the total crosses. Segregation patterns in the progenies corresponded with the chimeral types. Chlorophyll-deficient variation (resulting in variegation or the production of albino plants) was found at a frequency of 2.6%. These results show that chimeric tissues are actually in a mixed state and that either the ovary develops from more than two cells or else that variation occurs in the germ-cell layer. In interspecific chimeras between Ruby ball and Komatsuna (B. campestris) various types of chimeras generally showed low pollen fertility, few capsules, and low seed-setting. Progenies from selves (geitonogamy), open crosses and crosses with the two parental species produce a predominantly homogeneous genotype showing either the Ruby ball or the Komatsuna type. Only two crosses produced four interspecific hybrids which expressed variations in their morphological and isozymic characters.

Conventional B cells, not B1 cells, are the source of autoantibodies in chronic graft-versus-host disease.

B1 (CD5+) B cells have been implicated as a source of certain autoantibodies in several murine and human studies. We have previously shown in the lpr model of autoimmunity, however, that conventional B cells, not B1 cells, were the source of autoantibodies directed at chromatin, ssDNA, and IgG. In the current study, we have investigated the origin of autoantibodies in chronic graft-versus-host (GVH) disease, induced in nonautoimmune mice by transferring la-incompatible spleen cells. GVH mice develop multiple autoantibodies and significant kidney damage. Therefore, this model allowed us to examine the B cell subset involved in both autoantibody production and tissue injury. We used two protocols to establish B cell chimeras that possessed immunoglobulin heavy chain (lgh) allotype-marked peritoneal (B1-cell source) cells and bone marrow-derived (conventional B cell source) cells from nonautoimmune C57BL/6kh (B6) congenic mice. In both types of chimera, chronic GVH was induced by giving mice alloreactive T cells i.p. All of the subsequent anti-chromatin, RF, and anti-ssDNA autoantibodies were produced by the conventional B cells and not by B1 cells. In addition, glomerular immune complex deposits of both IgM and IgG originated from the conventional B cells and not from B1 cells. These findings thus parallel those from our previous work on autoantibodies in lpr, and extend those findings by demonstrating that antibodies within pathogenic immune complexes in the kidneys are also exclusively of conventional B cell origin.

Gld and lpr Hematopoietic Cell Transfers: Common and Different Serological Features of the C57BL/6 Chimeras

Homozygosity for either the lpr (lymphoproliferation) or the gld (generalized lymphoproliferative disease) mutation in mice causes the development of strikingly similar hyperglobulinemia and lymphoproliferative syndromes. Nevertheless, previous studies of various C57BL/6 chimeras obtained by reconstitution of irradiated recipients with hematopoietic cells (HC), differing at the bg, gld, lpr, and/or nu loci, showed that the lpr and gld syndromes had distinct etiologies. The [ lpr → lpr], [ gld → gld], and [ gld → wild ] chimeras developed lymphoid hyperplasia, while the [ lpr → wild, bg, or gld] and [ nulpr → wild or bg ] chimeras developed a severe persistent lymphoid aplasia. We now show that the serological status (immunoglobulin (Ig) levels and Ig isotype distribution) of the [ lpr → Ipr], [ gld → gld ], and [ gld → wild] chimeras were roughly equivalent to those of genetic lpr and gld mice. Despite their lymphoid aplasia, all the [ lpr → non- lpr] chimeras displayed surprisingly normal serum Ig levels, similar to [ wild → wild ] control chimeras, although always with some abnormal isotype profile. In fact, an early but transient increase of serum IgG1 levels was found in all [ lpr → wild, bg, or gld], [ Ipr → lpr], [ nulpr → wild or bg], [ wild → lpr], and [ gld → wild or gld ] types of chimeras. Despite a common early behavior, the host type and/or the gld or lpr HC origin may cause later divergences of the gld or lpr HC grafted chimeras.

Numerical simulation of mixing flows in agitated vessels with impellers and baffles

Abstract Mixing flows in an agitated vessel with impellers and baffles are computed using a dynamical multi-block method. In an example of a typical agitator with paddle impellers and baffles, the computational domain is divided into two blocks: the inner block containing rotating impellers; and the outer block containing baffles. In addition, only the inner block is rotated and the outer block is fixed. Thus, mixing phenomena are well-represented numerically. This method is also applied to a more complicated agitator with an inlet, an outlet and two-step impellers. In this example, a Chimera type of dynamical multi-block method with overlapping grids is used. It is then found that mixing flows are well-represented and the dynamical multi-block method works well in such an agitator with a complicated configuration.

Conventional B cells, not B-1 cells, are responsible for producing autoantibodies in lpr mice.

Mice homozygous for the lpr gene develop autoantibodies and polyclonal B cell activation similar to what is seen in human systemic lupus erythematosus patients. We have previously shown that an lpr-specific intrinsic B cell defect was necessary for autoantibody production in this model. In the current study, we have further defined these autoantibody-producing B cells. Two major subsets of B cells have been described. B-1 cells (CD5+ B cells) can be distinguished from conventional B cells on the basis of phenotype, cytokine secretion, gene expression, anatomical location, and function. In addition, B-1 cells have been implicated in autoimmunity in several murine and human studies. To address the question of which B cell subset produces autoantibodies in lpr mice, we used immunoglobulin heavy chain (Igh) allotype-marked peritoneal (B-1 cell source) and bone marrow (conventional B cell source) cells from lpr mice to establish B cell chimeras. We used two general approaches. In one, we reconstituted sublethally irradiated mice with B-1 cells of one allotype and bone marrow cells of another allotype. In the second method, we suppressed endogenous B cells in neonatal mice with allotype-specific anti-IgM antibody, and injected peritoneal cells of another allotype. After antibody treatment was stopped, the mouse's conventional B cells recovered, but the B-1 subset was only reconstituted by the donor. In both types of chimeras, antichromatin, rheumatoid factor, and anti-single stranded DNA (ssDNA) autoantibodies were produced by the conventional B cell bone marrow source. In addition, an age-related decrease in peritoneal B-1 cells was seen, even in unmanipulated lpr mice. These data show that lpr B-1 cells are not important producers of autoantibodies. Conventional B cells are the source of autoantibodies directed at chromatin, ssDNA, and IgG.

Vegetative and floral characteristics of interspecific Brassica chimeras produced by in vitro grafting

Interspecific Brassica chimeras (Brassica campestris+B. oleracea) were synthesized according to an in vitro graftculture method, and propagated by tissue culture of axillary buds or chimeric explants. A total of 127 regenerants obtained were investigated. The mericlinal chimera type was more easily produced than the other periclinal and revertant types. No sectorial chimera was produced. The flowering habit and inflorescence type of the chimeras were found to be controlled by the constitution of three tissue layers, but the petal shape and color were controlled only by the two outer tissue layers. Pollen viability of the chimeras were generally lower and more variable in parts than those of the parental types.

Demonstration of a phagocytic cell system belonging to the hemopoietic lineage and originating from the yolk sac in the early avian embryo.

It is well established that hemopoietic cells arising from the yolk sac invade the avian embryo. To study the fate and role of these cells during the first 2.5-4.5 days of incubation, we constructed yolk sac chimeras (a chick embryo grafted on a quail yolk sac and vice versa) and immunostained them with antibodies specific to cells of quail hemangioblastic lineage (MB1 and QH1). This approach revealed that endothelial cells of the embryonic vessels are of intraembryonic origin. In contrast, numerous hemopoietic cells of yolk sac origin were seen in embryos ranging from 2.5 to 4.5 days of incubation. These cells were already present within the vessels and in the mesenchyme at the earliest developmental stages analyzed. Two hemopoietic cell types of yolk sac origin were distinguishable, undifferentiated cells and macrophage-like cells. The number of the latter cells increased progressively as development proceeded, and they showed marked acid phosphatase activity and phagocytic capacity, as revealed by the presence of numerous phagocytic inclusions in their cytoplasm. The macrophage-like cells were mostly distributed in the mesenchyme and also appeared within some organ primordia such as the neural tube, the liver anlage and the nephric rudiment. Comparison of the results in the two types of chimeras and the findings obtained with acid phosphatase/MB1 double labelling showed that some hemopoietic macrophage-like cells of intraembryonic origin were also present at the stages considered. These results support the existence in the early avian embryo of a phagocytic cell system of blood cell lineage, derived chiefly from the yolk sac. Cells belonging to this system perform phagocytosis in cell death and may also be involved in other morphogenetic processes.

Analysis of the T cell repertoire for myelin basic protein in thymus‐grafted and other types of chimera: evidence that major histocompatibility complex molecules on accessory cells rather than T cell specificity mainly regulate susceptibility to autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease inducible in rodents by immunization of brain-specific antigens such as myelin basic protein (MBP). It is also well known that various strains of rats differ in their susceptibility to EAE upon active immunization. To elucidate the immune mechanisms of susceptibility and resistance to EAE, we first examined the T cell repertoire for MBP using thymectomized chimeras that possessed thymuses from EAE-susceptible (LEW) or EAE-resistant (BM) strains. It was revealed that T cell specificity of these chimeras was skewed toward that of the grafted thymus. Very interestingly, the chimeras bearing thymuses from the resistant strain developed severe EAE, keeping a hole in the encephalitogenic 68-88 sequence of MBP. These findings suggest that the strain-specific T cell repertoire itself is not involved in the regulation of EAE susceptibility. Furthermore, the analysis of the chimeras reconstituted with F1 T cells and marrow cells from various strains indicates that the major histocompatibility complex (MHC) molecules expressed on accessory cells primarily determine susceptibility or resistance to EAE. We finally showed, using various inbred and congenic rats carrying RT1l or RT1n, that susceptibility to EAE of rats carrying RT1l is heavily influenced by the background genes, whereas resistance to EAE of rats carrying RT1n is primarily regulated by the MHC molecules expressed on accessory cells without influence of the background genes.

Autoantibodies in chronic graft versus host result from cognate T-B interactions.

A chronic graft-versus-host reaction (GVH) induced in nonautoimmune mice causes a syndrome that closely resembles SLE. In this model, donor T cells react against incompatible host Ia structures and generate excessive help, which activates a subpopulation of self-reactive B cells. We have studied whether these self-reactive B cells are activated by direct interaction with alloreactive T cells or by nonspecific bystander effects. Two types of chimeras were made: double-parental chimeras, differing at both Ia and Igh allotype [B6.C20 + bm12----(B6.C20 x bm12)F1]; and control chimeras [(B6.C20 x bm12)F1----(B6.C20 x bm12)F1]. A chronic GVH syndrome was induced in the chimeras by infusion of B6 or bm12 spleen cells. Coombs and antichromatin autoantibodies were measured using Igh allotype-specific immunoassays. The double-parental chimeras that received bm12 cells made autoantibodies principally of the Igha allotype, indicating that the bm12 T cells interacted only with the Iab-bearing host B cells. Conversely, double-parental chimeras that received B6 cells made mostly Ighb autoantibodies, indicating direct cognate interaction with the Iabm12-bearing host B cells. The control chimeras made autoantibodies of both allotypes. These results indicate that autoantibodies in chronic GVH result from direct T-B interactions and not from nonspecific T cell-derived factors.

ALLOGENEIC VERSUS SEMIALLOGENEIC F1 BONE MARROW TRANSPLANTATION INTO SUBLETHALLY IRRADIATED MHCDISPARATE HOSTS

In models of tolerance associated with mixed lymphoid chimerism, depletion of Thy 1+ cells from the allogeneic donor inoculum may decrease the level of chimerism achieved and the capacity of donor cells to induce tolerance. To determine whether the apparent role of Thy 1+ cells in the facilitation of bone marrow engraftment and induction of skin graft tolerance is related to alloaggression, the capacity of fully allogeneic C57BL/6J, H-2b BM cells to establish mixed lymphoid chimerism and skin graft tolerance in sublethally irradiated (2.5 Gy x 3) BALB/c, H-2d hosts was compared with that of semi-allogeneic BALB/c x C57BL/6J F1 H-2d/b BM cells which genetically lack the potential for graft-versus-host reactivity against parental recipients. The levels of mixed chimerism observed with allogeneic and semi-allogeneic F1 BM cells were nearly identical: 21.0 +/- 9.7% of spleen cells in H-2b BM-injected and 18.6 +/- 8.8% of spleen cells in H-2d/b BM-injected H-2d hosts were of donor allotype. There was no difference in the fraction of hosts rendered tolerant to C57BL/6J, H-2b skin grafts by H-2b vs. H-2d/b BM at either excess (94% vs. 92% tolerant) or threshold (37% vs. 40% tolerant) numbers of donor cells. Spleen cells from both types of mixed chimeras failed to respond to donor antigens in MLR. Both H-2b and H-2d/b BM-injected H-2d hosts rejected third party C3H/HeJ, H-2k skin grafts and responded to third party stimulators in MLR. Although these nonspecific allo-immune responses were not as strong as the responses of normal animals, they were suppressed to an equivalent degree in both types of chimeras. Graft-versus-host disease, if present in irradiated H-2b BM-injected hosts, did not significantly affect survival compared with survival of irradiated H-2d/b BM-injected animals. These results suggest that the tolerizing capacity of allogeneic BM does not depend upon GVHD and that allogeneic and semi-allogeneic BM establish mixed lymphoid chimerism and induce skin graft tolerance by similar mechanisms across a complete MHC disparity in sublethally irradiated adult hosts.

The nature of the immune response (Ir) gene defect for pigeon cytochrome c in [B10.A(4R) × B10.PL]F1 mice

[B10.A(4R) x B10.PL]F1 mice are low responders to pigeon cytochrome c, while [B10.A(2R) x B10.PL]F1 and B10.A mice are high responders. The in vivo site at which the different allomorphs of the E alpha Ia molecule exert their Ir gene effect on the immune response to pigeon cytochrome c was examined by creating two different sets of radiation-induced bone marrow chimeras. [B10.A(4R) x B10.PL]F1(b.m.)----B10.A(irr.) chimeras, which possess antigen-presenting cells (APC) of the low responder, but whose T cells are educated in a high responder environment, were found to be low responders to pigeon cytochrome c. In contrast, B10.A(b.m.)----[B10.A(4R) x B10.PL]F1(irr.) chimeras, which possess APC of the high responder type, but whose T cells are educated in a low responder environment, responded to pigeon cytochrome c. Addition of B10.A APC to the first type of chimera, both prior to antigen priming and at the time of the secondary challenge in vitro, converted 50% of the animals to responders. Furthermore, [B10.A(4R) x B10.PL]F1 mice responded to pigeon cytochrome c if they were primed with a 10-fold greater antigen dose and restimulated in vitro in the presence of B10.A APC. These results suggest that the primary site of the Ir gene defect in this system is at the level of antigen presentation and not in the T cell repertoire.

Study on the possible factors influencing the expression of H-2 restriction specificity and Ir phenotype of antigen-specific proliferative T cells with various types of radiation chimeras

To better understand the factors described previously as influencing the manifestation of H-2 restriction specificity and Ir phenotype of T cells from radiation bone marrow chimeras, we also examined H-2 restriction specificity (Ir phenotype) of antigen (DNP-OVA, (T, G)-A-L, (H, G)-A-L)-specific proliferative T cells generated in various types of H-2 incompatible radiation chimeras prepared under our specific-pathogen-free (SPF) condition. The results indicated the following: (a) T cells generated in F 1 → parent bone marrow chimeras preferentially manifested host-type H-2 restriction specificity and Ir phenotype, regardless of the radiation dose (8.70 vs 11.59 Gy); (b) T cells recovered from twice-reconstituted F 1 → (P A → P B) chimeras manifested primary host (P B)-type Ir phenotype; (c) T cells which were recovered from (B10.Thy-1.1 × B10.BR.Thy-1.1) F 1 → parent (Thy-1.2) bone marrow chimeras and treated with anti-Thy-1.2 plus complement to deplete host-derived T cells still manifested preferentially the restriction specificity for host-type H-2; (d) P A-derived T cells which had differentiated in a fully allogeneic host (P B) environment of (P A + P B) → P B chimeras manifested fully allogeneic host-type Ir phenotype; (e) T cells from F 1 → parent chimeras that were prepared with 13-day fetal liver cells also manifested host H-2-restricted Ir phenotype; and (f) host preference for Ir phenotype of antigen-specific proliferative T cells was observed even in the case of F 1 → parent bone marrow chimeras reconstituted with “intact” bone marrow cells. The data suggest that thymic APCs, surviving host T cells or the source of stem cells (adult bone marrow vs 13-day fetal liver), do not necessarily play a significant role in the manifestation of H-2 restriction specificity and Ir phenotype of T cells generated in H-2 incompatible radiation chimeras.

Chimeric drift in the erythrocyte population in BALB/c-C57BL/10 and BALB/c-B10.D2 mice

Genotypic composition of the erythrocyte population of peripheral blood in 16 aggregation chimeras: BALB/c (H-2dd)----C57BL/10(H-2bb) and BALB/c(H-2dd)----B10.D2(H-2dd) was studied during 10 months. The proportion of cells of parental components was defined visually in the coat and by electrophoresis of allozyme variants at the Gpi-1 locus in blood. The similar increase of blood cells percentage was observed in blood of both types of chimeras with age. In chimeras the skin grafts of both parental types survive. Chimeric drift is not caused by H-2 haplotypes differences between cells of two strains or disturbance of immunological tolerance in the chimeric mice. We propose that chimeric drift results from interaction of hemopoietic cells of different strains in early stages of hemopoiesis.

Selective elimination of non-lpr lymphoid cells in mice undergoing lpr-mediated graft-vs-host disease.

The transfer of lpr BM stem cells into lethally irradiated non-lpr recipients (including the congenic MRL/+ differing only at the lpr locus) causes GVHD characterized by a wasting syndrome. In this study we investigated the interaction between the autoimmune (lpr) and normal (A-Thy) B, T, and RBC cell lineages in two types of radiation chimeras: MRL/lpr plus A-Thy----(MRL/lpr X A-Thy)F1 and MRL/+ plus A-Thy----(MRL/lpr X A-Thy)F1. Analysis of B cell repopulation by competitive RIA of serum Igh-1 allotype showed that both the MRL and the A-Thy donor cells initially engrafted. However, by 2 to 4 mo post-transplantation the normal A-Thy allotype was barely detectable (reduced greater than 2 orders of magnitude), whereas the autoimmune MRL/lpr allotype persisted at normal levels. Similarly, investigation of the donor origin of peripheral blood T cells by two-color flow cytometry showed that by 8 mo post-transplantation normal A-Thy T cells had been eliminated and only MRL/lpr T cells were present in the circulation. In contrast, erythrocytes from both the MRL/lpr and A-Thy donor strains successfully engrafted the F1 recipients and persisted until the termination of the study. Control chimeras transplanted with a mixture of MRL/+ plus A-Thy BM were stably engrafted with both donor strains in both the erythroid and lymphoid populations. Additional experiments in which either B6/lpr or MRL/lpr (and B6/+ or MRL/+ control) BM cells were transferred into (MRL/lpr X B6/+)F1 and (MRL/lpr X B6/lpr)F1 recipients demonstrated that the development of GVHD was not simply due to increased alloreactivity by the lpr donor cells. In these chimeras only the recipients heterozygous (but not homozygous) for the lpr gene developed lpr-GVHD, although both types of recipients had identical genotypes except at the lpr locus.

Embryonic origin of skeletal muscle cells in the iris of the duck and quail.

The origin of skeletal muscle cells in avian iris muscle was investigated by quantitative analysis of heterochromatin profiles at the electron-microscopic level in irides of six types of quail-duck chimeras. Each of the following tissues was transplanted into the head region from quail to duck between stages 9 and 10: cranial neural crest; trunk neural crest; midbrain and adjacent mesoderm; forebrain; forebrain without neural crest; and forebrain without neural crest and mesoderm. The average ratio of heterochromatin profile to nucleus profile in iris skeletal muscle cells was high (quail type) in the dorsal iris, but low (duck type) in the ventral iris of the chimeras resulting from isotopic transplantation of cranial neural crest. Heterotopic transplantation of trunk neural crest to cranial position resulted in failure of development of skeletal muscle cells in the dorsal iris, but not in the appearance of skeletal muscle cells in the ventral iris. The average ratio of heterochromatin profile to nucleus profile in iris skeletal muscle cells was high in the chimeras resulting from transplantation of midbrain region and the chimeras resulting from transplantation of forebrain region, intermediate in the chimeras resulting from transplantation of forebrain region without neural crest, and low in the chimeras resulting from transplantation of forebrain region without neural crest and mesoderm. These results indicate that the skeletal muscle cells in the dorsal iris are of cranial neural crest origin while those in the ventral iris are not, and could possibly arise from cranial mesoderm.

Characterization of virus-specific cytotoxic T cell clones from allogeneic bone marrow chimeras.

We established several H-2-restricted lymphocytic choriomeningitis virus (LCMV)-specific cytotoxic T cell clones from spleens of virus-primed C57BL/6 or C57BL/10 (H-2b) and B10.BR (H-2k) mice and from allogeneic C57BL/10----B10.BR and B10.BR----C57BL/10 bone marrow chimeras. Two T cell clones of H-2b origin and restricted to H-2b, 3 of H-2k origin and restricted to H-2k were compared with two clones each derived from the two types of chimeras. Their surface phenotype was found to be Lyt-2+, L3/T4- and KJ16-133+ (2 of 9). Clones from chimeras expressed bone marrow donor H-2 and are restricted to the recipient H-2. H-2k-restricted clones were all specific for Kk whereas all H-2b-restricted clones were specific for Db. These restriction specificities could be further defined by the blocking activity of various monoclonal anti-H-2 antibodies. Interestingly the anti-H-2Db antibodies blocked the restricted virus-specific killing activity of the clones derived B10.BR----C57BL/10 chimeras much more effectively than the activity of the clones derived from conventional H-2b mice. The various clones differed with respect to their fine specificity for LCMV strains. The 3 clones of conventional B10.BR origin only recognized LCMV-WE but not LCMV-Armstrong, Aggressive or Docile; H-2b-restricted conventional clones recognized target cells infected with all LCMV strains except LCMV-UBC-Docile; the T cell clones from the bone marrow chimeras recognized with one exception all LCMV strains tested.

Clones of B lymphocytes in individual follicles of the bursa of Fabricius.

To discover whether individual bursal follicles can contain clones of B lymphocytes, we estimated the numbers of lymphoid cell precursors populating single follicles in two types of chicken chimera. The first type was produced by establishing parabiotic connections between blood vessels of embryo chorioallantoic membranes. Under these conditions, and most likely during normal development, most follicles are populated by more than one, but less than ten, precursor cells. However, in a second type of chimera, a cyclophosphamide-treated chick reconstituted with normal bursal cells, most follicles in the reconstituted bursa are clonal (their lymphocytes are derived from a single precursor cell). Individual follicles can readily be isolated from bursae of reconstituted birds and should be useful in studies of B cell development.

Genetic analysis of instability inPetunia hybrida

InPetunia hybrida frequent mutations of unstable alleles give rise to different types of periclinal chimeras. If genes expressed in the epidermis, such as the geneAn1 for flower colour, are concerned, mutations in the dermal layer of the shoot apex will result in changes in the phenotype but not in the offspring. Mutations in the subdermal layer will not lead to an altered phenotype, but to changes in the sporogenous tissues and, thus, to deviating segregations in progenies. Therefore, in crossing experiments with such an unstable mutant, it is always necessary to take the possibility into account that the plant may be a chimera, so as to prevent an incorrect interpretation of the recorded segregational ratios. Mutations of unstable alleles expressed in the mesophyll, such as geneYg3 for leaf colour, also give rise to chimeras. In such instances, however, a change in phenotype always involves a change in segregational ratios as well, since both the mesophyll and the sporogenous tissues are derived from the subdermal layer of the shoot apex.

Anti-viral immune response of allogeneic irradiation bone marrow chimeras: cytotoxic T cell responsiveness depends upon H-2 combination and infectious agent.

Allogeneic irradiation bone marrow chimeras C57BL/10 (H-2b) leads to B10.BR (H-2k) and B10.BR (H-2k) leads to C57BL/10 (H-2b) were raised under specific pathogen-free (SPF) conditions; they survived very well and were healthy under SPF for 3-4 months and subsequently, under conventional housing conditions, for 1 to 8 months. Their immune response against third-party alloantigens was comparable with that of controls. Anti-vaccinia virus responses were very low when compared with syngeneic control chimeras or unmanipulated control animals; if anti-vaccinia virus cytotoxic T cell reactivity was measurable, it was specific for the bone marrow donor, rather than the recipient thymic H-2 type. In contrast, the anti-LCMV (lymphocytic-choriomeningitis virus) response was excellent and comparable to that in controls for B10.BR (H-2k) leads to C57BL/10 (H-2b) chimeras, but was completely absent for C57BL/10 (H-2b) leads to 10.BR (H-2k) chimeras. LCMV-specific cytotoxic effector T cells from B10.BR leads to C57BL/10 chimeras were restricted entirely to recipient H-2b. In contrast to the asymmetric cytotoxic T cell response, both types of chimeras developed good primary footpad swelling reactions after local infection, which arose somewhat slower with LCMV than in control of chimeras. The capacity to control infection by Listeria monocytogenes was excellent for all controls and B10.BR leads to C57BL/10 chimeras but apparently absent in C57BL/10 leads to B10.BR chimeras. Differentiation of T cell restriction specificity for thymic H-2 is apparently most efficient, but it remains unclear whether the observed asymmetry reflects exaggerated immune response regulation in H-2-incompatible stem cell-thymus chimeras or differential cross-reactivities between restricting transplantation antigens.

Chimeras and Variegation: Problems in Propagation

Abstract Chimeras are defined as organisms containing 2 or more genetically distinct cell types. Horticulturally, the most important type of chimera is the variegated leaf chimera in which the pale (yellow or white) leaf areas differ from the green leaf areas by a gene (or genus) for chlorophyll, carotenoids, or a chloroplast protein (10, 30, 31). Likewise, most of what is known about chimeras in general is based upon studies of these variegated plants.