bluuebunny/crossref_metadata_2025 huggingface dataset:
THE RATE OF DIVISION OF ANTIBODY-FORMING CELLS DURING THE EARLY PRIMARY IMMUNE RESPONSE
Authors: Rowley Donald A. , Fitch Frank W. , Mosier Donald E. , Solliday Susan , Coppleson Lionel W. , Brown Barry W.
Published: June 2004

Mitotic blocking agents, colchicine or Velban, were used to estimate cycle times of spleen cells which release hemolysin for sheep erythrocytes (plaque-forming cells). The cells were obtained either from rats immunized with sheep erythrocytes or from cultures of mouse spleen cells immunized in vitro with the same antigen.

2, 3, or 4 days after immunization, animals or cell cultures were treated with mitotic blocking agents for periods of time ranging from 2.5 to 7 hr; plaque-forming cells were then enumerated. Decreased numbers of plaque-forming cells were found after such treatment. The extent of reduction was a function of duration of the drug treatment and the method of immunization, but was independent of the time after immunization. The evidence presented is consistent with premises that: (a) plaque-forming cells in mitosis do not release sufficient antibody to be detected, (b) mitotic blocking agents, by arresting plaque-forming cells in metaphase, prevent not only detection of these cells but also the increase in number of plaque-forming cells which would have resulted from cell division, (c) mitotic blocking agents do not affect release of antibody by cells in interphase.

Cell cycle times, based on the extent of reduction of plaque-forming cells per unit time of drug treatment, were estimated using a mathematical model appropriate for an exponentially increasing population of cells. Cell cycle times estimated using the mitotic blocking agents agreed well with cell doubling times calculated from the increase in plaque-forming cells occurring 1–4 days after immunization. Increased responses produced by higher antigen doses or treatment of immunized animals with an adjuvant resulted from an increased rate of division of responding cells and their progeny.

The results are consistent with a cell selection theory of antibody formation. Antigenic stimulation causes relatively few cells to proliferate and to synthesize antibody; apparently the magnitude of the response is dependent primarily on the rate of division of responding cells. It is suggested on the basis of observations of in vitro-immunized cell cultures that the rate of division of responding cells may be dependent on the rate of interaction between two cell types, both of which are essential for the in vitro plaque-forming cell response.
STUDIES ON THE MECHANISM OF TUMOR INHIBITION BY L-ASPARAGINASE
Authors: Broome J. D.
Published: June 2004

L-asparaginases of agouti serum and Escherichia coli cause a profound lowering in the level of free asparagine in the blood of treated mice and also in the tissues. During treatment, normal tissues and resistant 6C3HED lymphomas survive unharmed with intracellular asparagine levels which are critically low for sensitive lymphomas. An explanation for this contrast between the two types of lymphoma is provided by the finding that resistant cells have not only a higher asparagine synthetic capacity than sensitive cells but appear able to utilize endogenous asparagine preferentially for protein synthesis. Cell-free extracts of resistant cells contain an asparaginase synthetase, but this is not found in preparations from sensitive cells.
THE PRIMARY IMMUNE RESPONSE IN MICE
Authors: McMaster Philip D. , Franzl Robert E.
Published: June 2004

The effects of a single injection of a bacterial endotoxin on the cellular changes of a primary immune response to a standard dose of sheep red blood cells were studied in the spleens and mesenteric lymph nodes of mice. Daily histological comparisons of these organs in mice, injected with endotoxin, or with antigen, or both, showed that endotoxin given simultaneously with sheep red blood cells, as antigen, significantly enhanced all of the cellular changes that appear in the mesenteric lymph nodes and spleens of mice that form antibody when that antigen is given alone. First, in the white pulp of the spleens and cortical regions of the nodes, there appeared an early and excessive proliferation of the large pyroninophilic cells which seems to be responsible for the earliest formation of antibody, as judged by this work and that of others cited in the body of the paper. Polymorphonuclear cells invaded the spleens of these animals early after simultaneous challenge with antigen and endotoxin, and in far greater numbers than have ever been seen in mice given the same antigen without endotoxin. "Activated" germinal centers formed in the lymphoid tissue either 1 day before the appearance of antibody in the blood stream or on the same day, and they became larger than in the mice given antigen only. On the other hand, these specific and characteristic cellular changes failed to appear in mice prevented from forming any antibody at all by injections of endotoxin given 2 days before the antigenic challenge.

These findings are discussed in the light provided by data from recent reports of others as well as in the light of the accompanying paper (1) which demonstrated not only the enhancement of antibody formation following simultaneous injections of antigen and endotoxin, as already known, but a totally unexpected, complete suppression of its formation when endotoxin was given 2 days before antigen.
SEROLOGICAL ANALYSIS OF THYMUS AND SPLEEN GRAFTS
Authors: Schlesinger Michael , Hurvitz Dahlia
Published: June 2004

Thymus and spleen grafts from neonatal C57BL mice were implanted beneath the kidney capsule of (A x C57BL) F1 hybrids. At various intervals after implantation, the grafts were analyzed serologically. Cells of each graft were tested for the presence of cells of host origin, TL (thymus-leukemia) antigenicity, and sensitivity to the cytotoxic effect of guinea pig serum (GPS).

Thymus grafts showed partial repopulation by host cells 11 days after grafting, and some grafts were completely repopulated by host cells 13 days after grafting. All thymus grafts were fully repopulated 18 days after grafting. With one exception, thymus grafts contained no significant number of TL-positive cells within 14 days after grafting. TL-positive cells appeared in thymus grafts examined 15 days after implantation, and their number increased up to the 18th day after implantation. Cells residing in thymus grafts remained sensitive to GPS throughout the period of observation. The acquisition of thymus-distinctive serological properties by host cells repopulating thymus grafts was similar in intact and in thymectomized recipients.

Spleen grafts were completely repopulated by host cells as early as 8 days after grafting. The cells residing in spleen grafts remained TL-negative throughout the period of observation, and were refractory to the cytotoxic effect of GPS.

It is thus apparent that, while both spleen and thymus grafts are invaded by TL-negative cells, only those entering the thymus acquire the antigen. The nature of the process by which the thymus endows thymus-distinctive properties on cells entering it is discussed.
HIGH-DOSE DELAY OF THE IMMUNE RESPONSE
Authors: Iványi J. , Maler M. , Wudl L. , Sercarz E.
Published: June 2004

The continuation of the primary and secondary antibody response to human serum albumin (HSA), induced in vivo, was followed in explanted chicken spleen fragments. The effect of actinomycin D (AMD) on the in vitro response was studied in spleens from chickens injected with various doses of HSA and removed at differing intervals after injection.

The antibody response of "early spleen" cultures was AMD-sensitive, while cultures of spleens removed later were AMD-resistant. It was suggested that this shift represented the development of cells with in vivo preformed RNA involved in specific immunoglobulin synthesis.

With increasing doses of HSA, the AMD-sensitive phase was prolonged, suggesting the delay of mRNA formation or some other AMD-inhibitable process in vivo. With large doses of HSA, the immune response in vitro was decreased, starting after a 1–2 day delay and not occurring in the presence of AMD. Massive doses of HSA completely inhibited the continuation of the response in vitro by spleen fragments removed between the 2nd and 5th day after injection.

The results point to the controlling role of antigen dose in determining the onset of macromolecular synthesis during immunocyte maturation.
GENETIC CONTROL OF THE ANTIBODY RESPONSE IN INBRED MICE
Authors: McDevitt Hugh O. , Tyan Marvin L.
Published: June 2004

The transfer of spleen cells from (C3H x C57Bl/6) F1 mice, capable of responding to (T,G)-A--L, into irradiated C3H parental recipients, normally incapable of responding to (T,G)-A--L, transfers the ability to make either a primary or secondary immune response to this synthetic polypeptide antigen. This localizes the genetic control of the ability to respond to the spleen cell population and indicates that the genetic control is exerted upon a process directly related to antibody formation. Studies with congenic strains of mice and linkage studies in segregating backcross populations show that the ability to respond to (T,G)-A--L and (H,G)-A--L is linked to the H-2 locus and can thus be localized to the IXth mouse linkage group.

Note Added in Proof: Of the three possible recombinant animals noted in Tables IV and V, two were infertile. The third animal was not a recombinant, since progeny testing and reimmunization showed that this animal was an H-22/H-2k heterozygote capable of responding well to (T,G)-A--L.
RELATIONSHIP OF GERMINAL CENTERS IN LYMPHOID TISSUE TO IMMUNOLOGICAL MEMORY
Authors: Wakefield J. D. , Thorbecke G. J.
Published: June 2004

The fate, proliferation, and developmental potentialities of cell suspensions made from white pulp containing large germinal centers have been studied in the mouse by transfer of cells labeled with thymidine-3H to lethally irradiated, syngeneic recipients. Radioautographic analyses were made using both smears and sections of a variety of tissues. Thymidine-3H-labeling patterns of white pulp showed that, initially, labeling occurred in a majority of blast and "intermediate cells" but in very few or no small lymphocytes. After intravenous transfer, most of the labeled cells localized in the lymphoid tissues of spleen, lymph nodes, and Peyer's patches. Few cells migrated to the thymus, lung, liver, and intestinal mucosa.

Both after intravenous and after intraperitoneal transfer there was a rapid increase in the incidence of labeled small lymphocytes and a decrease of labeled blasts and intermediate cells. This was accompanied by an increase in the grain count of the small lymphocytes and a progressive decrease in the grain counts of the blast cells. Exposure of nonlabeled donor cells to thymidine-3H at various time intervals after transfer indicated that dividing cells were present early after transfer but that their incidence progressively decreased. Between 24 and 48 hr, very little cell division was detectable.
RELATIONSHIP OF GERMINAL CENTERS IN LYMPHOID TISSUE TO IMMUNOLOGICAL MEMORY
Authors: Wakefield J. D. , Thorbecke G. J.
Published: June 2004

White-pulp cells and whole spleen from donor mice immunized with sheep erythrocytes were transferred intravenously to heavily irradiated mice. The numbers of plaque-forming cells and the amount of hemagglutinating antibody produced after reexposure to antigen were measured.

When reexposure to sheep erythrocytes was delayed, a much greater response occurred in the transferred cells. Peak responsiveness was reached at 24 hr after transfer. This "lag effect" was greatly reduced by repeated injections of 5-bromodeoxyuridine into the recipient mice prior to challenge with antigen. It was therefore concluded that much of the increase in responsiveness was due to a proliferation of "primed" cells after cell transfer. The fact that a significant response was given by the transferred cells in spite of 5-bromodeoxyuridine treatment suggested that some of the primed cells were nondividing.

White pulp was a much richer source of responsive cells than was whole spleen.
STUDIES ON THE INDUCTION OF TOLERANCE OF THE H-Y ANTIGEN IN MICE WITH NEONATAL SKIN GRAFTS
Authors: Silvers Willys K.
Published: June 2004

In contrast to the uniform rejection of adult male skin isografts by C57BL/6 females, neonatal male skin isografts are frequently accepted. Moreover, 50% of all females which accept a neonatal male skin graft for 50 days accept a subsequent adult male skin graft as well.

This ability of neonatal skin to produce tolerance has been investigated under a variety of experimental conditions. The results indicate: (a) Even when a newborn male skin graft is transplanted concomitantly with an adult graft, it can produce tolerance of the latter although it is less effective in this regard than when transplanted beforehand. (b) The continued exposure of the host to the newborn graft is vitally important in maintaining the unresponsive state; and most females deprived of these grafts for 50 days manifest an immune response when challenged with adult male skin. (c) Newborn male skin isografts raised on adult females are not as antigenic as normal male skin grafts. (d) Occasionally, even a presensitized female can be rendered tolerant by grafting with neonatal male skin. (e) Neonatal male skin grafts are not accepted when transplanted to the spleens of adult females although they may occasionally induce tolerance of a subsequent orthotopic adult male skin graft. The failure of these intrasplenic grafts to survive can be attributed at least partly to their small size since orthotopic grafts of comparable size usually do not survive. (f) Females bearing neonatal male skin grafts are not perceptible cellular chimeras.

Because the unresponsive condition induced with neonatal skin is similar to that which results from multiparity, this latter condition has also received attention. In this regard it has been established that unlike the removal of a neonatal male skin isograft, the delayed grafting of isolated females with a previous history of multiparity does not result in many of them manifesting what may be considered an immune response. However, this delay in grafting does seem to impair the tolerance multiparity produces.

The results are discussed in relation to other methods of producing tolerance in adult animals.
ALTERATIONS IN THE MOUSE CECUM AND ITS FLORA PRODUCED BY ANTIBACTERIAL DRUGS
Authors: Savage Dwayne C. , Dubos René
Published: June 2004

Addition of penicillin, Terramycin, or kanamycin to the drinking water of adult mice rapidly induced in them an enlargement of the cecum. In all animals, this occurred within 12 hr after the beginning of drug administration—the effect being most pronounced with penicillin. The cecums remained enlarged and generally continued to increase in size as long as the antibacterial drugs were administered.

The increase in wet weight of the cecums was due primarily to an accumulation of water in the lumens during the first 24–48 hr of drug administration. At that time, there were no detectable histological changes in any case, but the bacteriological picture differed from drug to drug. The cecums were free of bacteria in animals receiving penicillin, fusiform-shaped bacteria and bacteroides were present in those receiving Terramycin, and lactobacilli and bacteroides in those receiving kanamycin. After the initial 48 hr, an abundant and complex secondary microflora developed in all treated animals, its composition being characteristic for each type of antibacterial drug.

When penicillin was administered for 2 wk, the cecal weights and microbial populations did not return to normal levels for over 14 days after discontinuance of the drug. This recovery period could be shortened to 10 days by giving the mice food contaminated with cecal homogenates prepared from normal animals. A period of 7 or 8 days was required for the cecal weights and microflora to reach normal levels when the administration of penicillin lasted only 24 hr; this period could not be shortened by giving the animals contaminated food.

The effects of drugs on the size and bacterial contents of the cecum have been discussed in the light of earlier findings concerning the characteristics of the huge cecums uniformly found in germfree mice. Taken together, these observations support the hypothesis that certain elements of the intestinal microflora—not yet completely identified—play an essential role in maintaining the integrity of the water-transport mechanism in the intestinal epithelium.
CYTOLOGY OF IMMUNOLOGIC MEMORY
Authors: Bosman Cesare , Feldman Joseph D.
Published: June 2004

Pairs of rats were immunized with keyhole limpet hemocyanin (KLH) and simultaneously labeled with thymidine-methyl-3H or 5-iodo-2'-deoxyuridine-125I. From 10–50 days later, their lymphoid organs were examined 3 days after anamnestic stimulation with KLH or after primary injection of BGG. Light and electron microscopic study of the labeled cells revealed that immunologic memory resided in the mature resting monoribosomal lymphocyte which, upon stimulation, transformed to an immature polyribosomal lymphocyte and mitotically active blast cell. These latter elements differentiated into plasma cells directly or after mitosis.
PATHOGENETIC MECHANISMS IN EXPERIMENTAL IMMUNE FEVER
Authors: Root Richard K. , Wolff Sheldon M.
Published: June 2004

When rabbits sensitized to human serum albumin (HSA) are challenged intravenously with specific antigen, fever develops and two transferable pyrogens can be demonstrated in the circulation. The first appears prior to the development of fever and has properties consistent with soluble antigen-antibody complexes. These have been shown to be pyrogenic when prepared in vitro and to produce a state of febrile tolerance when repeatedly administered. The second pyrogen, demonstrable during fever in donor rabbits, appears to be similar to endogenous pyrogen described in other experimental fevers. It is postulated that the formation of antigen-antibody complexes constitutes an important initial phase of the febrile reaction in this type of immune fever.
ANTIBODIES TO INTESTINAL MICROVILLOUS MEMBRANES
Authors: Mackenzie Iain L. , Donaldson Robert M. , Kopp William L. , Trier Jerry S.
Published: June 2004

Microvillous membranes isolated from the distal, but not proximal, half of hamster small bowel induced in rabbits the formation of antisera which inhibited intrinsic factor-mediated uptake of vitamin B12 by hamster brush borders. The extent of inhibition was directly proportional to the concentration of antiserum, and an excess of IF-bound vitamin B12 could overcome the inhibitory effect. The inhibitory factor was absorbed from antisera by brush borders isolated from the distal, but not proximal, half of the hamster intestine. Fractionation of antisera by gel filtration and DEAE-cellulose chromatography established that immunoglobulin G contained the inhibitory factor. Antisera capable of completely blocking uptake of IF-bound vitamin B12 did not react with hamster IF or with the IF-vitamin B12 complex, did not inhibit brush border disaccharidase activity and did not impair glucose transport by everted sacs of hamster intestine. These results demonstrate that an antibody to distal microvillous membranes competes with the IF-vitamin B12 complex for a specific binding site or receptor located on the surface of distal hamster intestine.
CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE
Authors: Shearer G. M. , Cudkowicz G. , Connell Mary St. James , Priore R. L.
Published: June 2004

Spleen cell suspensions of unprimed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice. In the presence of antigen (sheep erythrocytes) these precursors, called antigen-sensitive units, gave rise to progeny cells secreting specific antibody. We studied quantitatively the production of cells releasing IgM hemolysins (direct plaque-forming cells), IgG hemolysins (indirect plaque-forming cells), and hemagglutinins (cluster-forming cells). We found that each of these immunocyte populations was distinct, i.e., that cells releasing agglutinins did not, as a rule, release hemolysins, and vice versa. We also found that cell populations secreting IgM hemolysins did not shift, under certain experimental conditions, to the production of IgG hemolysins during the primary immune response.

By transplanting graded numbers of spleen cells, we succeeded in limiting to one or a few the number of antigen-sensitive units that reached the recipient spleen. We estimated thereby the frequency of antigen-sensitive units in donor cell suspensions and tested their potential for production of immunocytes of more than one type. Our results indicated that antigen-sensitive units were unipotent for they displayed in the spleens of unprimed donors the same restrictions of function and heterogeneity (antibody-specificity differentiation, antibody-class differentiation) found among antibody-forming cells. Furthermore, antigen-sensitive precursors for direct plaque-forming cells, indirect plaque-forming cells, and cluster-forming cells were detected in the spleens of unprimed mice in different frequencies, i.e., 1 in ∼ 106, 1 in ∼ 7 x 106, and 1 in ∼ 19 x 106 spleen cells, respectively.

We concluded that relatively advanced differentiation of potentially competent cells occurs before sheep erythrocyte administration. The relevance of this finding for the broad spectrum of immunologic reactivities and for the heterogeneity of antibody responses to given antigens was discussed.
EFFECT OF REMOVAL OF CHOLESTEROL DIET UPON SERUM SICKNESS-CHOLESTEROL-INDUCED ATHEROSCLEROSIS
Authors: Van Winkle M. , Levy L.
Published: June 2004

In this report, the role of vascular allergy (i.e., hypersensitivity) in the potentiation of atherogenesis has been studied. In order to accomplish this, bovine serum albumin (BSA) was administered to rabbits in quantities sufficient to cause the occurrence of serum sickness (a type of hypersensitivity known to cause injury to the endothelial linings of certain blood vessels). This was immediately followed by the feeding of a special cholesterol-supplemented diet, which is known to be capable of initiating a high incidence of atheromatous disease in rabbits after prolonged feeding. Results indicated that those animals which received the combined treatment developed an incidence of pathology after only 2 wk of special diet which was not equaled in the diet-only control groups until they had been treated for 4 wk. This indicated that vascular allergy could potentiate lipemia-induced atherogenesis in the rabbit, and was in confirmation of an earlier study of a similar nature. Indeed, because of the relatively mild vascular injury caused by a single injection of BSA, it would seem as though vascular hypersensitivity was extremely effective in the potentiation of atherogenesis.

In addition, these results may have given some indication of the degree of vascular injury necessary for the induction of irreversible atheromatous disease. While the incidence of lesions in serum sickness controls was seen to decrease with passage of time after BSA challenge, it appeared to increase after cessation of treatment in those animals which received the combined treatment of BSA plus 2 wk of cholesterol-supplemented diet. It would therefore appear that the atheromatous lesions seen as early as 2 wk after initiation of the experiment may already have been irreversible in terms of the resolution of established pathology.
THE SECOND COMPONENT OF HUMAN COMPLEMENT: ITS ISOLATION, FRAGMENTATION BY C'1 ESTERASE, AND INCORPORATION INTO C'3 CONVERTASE
Authors: Polley Margaret J. , Müller-Eberhard Hans J.
Published: June 2004

A method has been described for the purification and isolation of the second component of complement (C'2) from human serum. The protein is a ß1-globulin with an approximate molecular weight of 117,000. Immunochemical analysis using a variety of specific antisera, including a monospecific antiserum to the isolated protein, indicate that the C'2 protein represents a heretofore unrecognized human serum constituent. Isolated C'2 contained 2 x 109 "effective molecules" per microgram and 1000 hemolytically active C'2 molecules were required to produce a single hemolytically effective C'2 site on erythrocytes undergoing immune cytolysis. C'1 esterase treatment of C'2 resulted in reduction of both its electrophoretic mobility and its molecular size, the latter observation indicating fragmentation of the molecule. Direct evidence was presented for the physical presence of C'2 as an integral part of the enzyme C'3 convertase.
SYNTHESIS OF THE FIRST COMPONENT OF HUMAN COMPLEMENT IN VITRO
Authors: Colten Harvey R. , Gordon James M. , Borsos Tibor , Rapp Herbert J.
Published: June 2004

Isolated segments of human colon and to a lesser extent ileum were capable of synthesizing hemolytically active C'1. This conclusion was based on the following evidence:

After elimination of C'1 from tissue with EDTA, we found that segments of the intestinal tract in short-term organ culture showed a 50–1000-fold increase in C'1 activity. The rate of production of C'1 in human intestine was highly temperature dependent; C'1 production was reversibly inhibited by puromycin and actinomycin D. Furthermore, 14C-labeled amino acids were incorporated into molecules which behaved like C'1. No significant C'1hu synthesis was observed in isolated segments of jejunum, stomach, liver, kidney, lung, spleen, lymph node, and thymus.
ISOLATION AND CHARACTERIZATION OF PERMEABILITY FACTORS FROM RABBIT NEUTROPHILS
Authors: Ranadive N. S. , Cochrane C. G.
Published: June 2004

Four basic proteins that increase vascular permeability have been isolated in purified form from rabbit neutrophilic granules. These proteins are termed band 1, 2, 3, and 4 protein according to their electrophoretic migration in acrylamide gel. Molecular weights of band 1 and 2 protein derived from amino acid composition were 4800 and 5300, respectively. These values are in good agreement with those obtained for these proteins by gel diffusion techniques. The molecular weight of band 3 protein was also in the range of 5000 by the latter technique. The molecular weight of band 4 protein determined by ultracentrifugal analysis and amino acid composition was 12,000.

Although all four proteins had the capacity to induce immediate increase in vascular permeability, only band 2 protein was found to release histamine from isolated rat peritoneal mast cells. Furthermore, it has been shown that the permeability-inducing activity of band 2 protein can be inhibited by pretreating rabbits with antihistamine. Band 2 protein did not release histamine from rabbit platelets and depletion of rabbit platelets from the circulation had no influence on the permeability-inducing activity of this protein.

Band 1, 3, and 4 proteins did not release histamine from isolated rat peritoneal mast cells and their capacity to increase vascular permeability remained unaffected by treatment of rabbits with antihistamine.

These investigations suggest that the histamine-releasing activity of band 2 protein is a specific phenomenon and is associated with particular amino acid grouping or spacial configuration of the molecules. By the same token, the increase in vascular permeability induced by the nonhistamine-releasing band 1, 3, and 4 proteins represents a specific phenomenon (or phenomena) not particularly related to the over-all charge of these molecules.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Lee Chi-Jen , Dubos René
Published: June 2004

A lasting depression of body weight was consistently produced in SPF mice by infecting them orally 2 days after birth with a nonlethal, bacteria-free filtrate, prepared from the intestine of young SPF mice previously infected with an unidentified agent.

Neonatal infection caused a decrease of muscle DNA and of muscle and brain protein in the adults. No other effect was detected in the chemical composition of various organs.

Incorporation of 14C-amino acid into the acid precipitable fractions of liver, kidney, muscle, and brain was lower in infected than in control animals. No difference in incorporation was recognized in the thymus and spleen.

The free amino acid pool of adults, measured as blood levels of free amino nitrogen, was decreased by neonatal infection.

Surprisingly, the food intake of young animals infected neonatally was higher than that of the controls, measured on the basis of body weight. Their fecal excretion of nitrogen was also higher.

The comparative responses of infected and control adults to a stressful situation was measured by giving them intravenously the antituberculous vaccine BCG. Under these conditions, the mice infected neonatally excreted some 20% more nitrogen in their urine and 40% more in their feces than did the controls.

The mechanisms through which neonatal infection caused a lasting weight depression are discussed in the light of these metabolic findings.
FURTHER STUDIES ON THE γG-HEAVY CHAIN GENE COMPLEXES, WITH PARTICULAR REFERENCE TO THE GENETIC MARKERS Gm(g) AND Gm(n)
Authors: Natvig J. B. , Kunkel H. G. , Yount W. J. , Nielsen J. C.
Published: June 2004

The recently described Gm (g) and Gm (n) genetic markers of the γG3- and γG2-subgroups of γ-globulin were characterized in detail primarily through studies of myeloma proteins, their polypeptide chains and fragments. Antisera derived from rabbits, non-human primates and rheumatoid arthritis patients gave identical results. This contrasted with the Gm (b) system where the rabbit antisera react with a different genetic determinant (b0) than the sera from rheumatoid arthritis patients (b). The Gm (g) and Gm (n) antigens were detected both by precipitin analysis and by hemagglutination inhibition. The Gm (g) antigen was not associated with any of the other genetic antigens of the γG3-proteins which all belonged in the Gm (b) class. The genes for the latter were always allelic to the gene coding for Gm (g), with that for Gm (b0) constantly present when that for Gm (g) was absent.

The Gm (g) and Gm (n) markers were of particular value in tracing the various gene complexes made up of the closely linked subgroup genes. Further support was gained for the concept that the different gene complexes of various population groups arose primarily through crossing-over. The Gmg and Gmb genes for the γG3-subgroup were extremely closely linked to those for the γG1-subgroup. However the Gm (n) marker indicated that the γG2-subgroup genes were probably further separated on the chromosome. Additional evidence was obtained for the γG2-γG3-γG1-order of the subgroup cistrons.

Among the wide range of gene complexes a new type (γG2,—,γ/G1) was described. This complex appeared to have a deletion of the γG3-cistron. Lower levels of γG3-globulin were found in the sera of the individuals with this gene in the heterozygous state. The possibility that this unusual complex arose through an unequal nonhomologous crossing-over is discussed.
RELATION BETWEEN EPSTEIN-BARR VIRAL AND CELL MEMBRANE IMMUNOFLUORESCENCE OF BURKITT TUMOR CELLS
Authors: Klein G. , Pearson G. , Nadkarni J. S. , Nadkarni J. J. , Klein E. , Henle G. , Henle W. , Clifford P.
Published: June 2004

A comparison was made of the immunofluorescence tests for detection of cell membrane and Epstein-Barr virus antigens in cells from Burkitt tumor biopsies or continuous cultures derived therefrom. On the whole, cell membrane fluorescence in established lines appeared to depend not only upon the presence of EBV but to a considerable degree also upon the extent of the persistent viral infection. There was no constant relationship, however, between the results of the two tests and exceptions to the rule were noted. These observations indicate that different antigens are involved in the two tests. Biopsy cells in general and young cultures may reveal strong MIF activity but few, if any, EBV-positive cells. The reverse, the presence of relatively large numbers of EBV antigen-containing cells in the absence of significant MIF reactions, was also noted on occasion in a few established cultures. The possible interpretations of these findings have been discussed.
THE SUBCELLULAR DISTRIBUTION OF ANTIGEN IN MACROPHAGES
Authors: Kölsch E. , Mitchison N. A.
Published: June 2004

The intracellular fate of phagocytosed antigens in cells from peritoneal exudate in CBA mice has been studied by using 126I and 131I labeled antigens. After uptake of labeled antigen, cells were homogenized and the subcellular fractions were analyzed by isopycnic centrifugation in a sucrose gradient.

The uptake of heat-denatured BSA (c BSA) by these cells in vivo is 3.5 µg/mg c BSA injected/108 cells. The uptake by cells in animals which were exposed 2 days earlier to 900 r whole body irradiation is slightly lower but does not differ significantly. 90% of the phagocytosed material is degraded within 2–3 hr, the residual 10% is retained at least over an 8 hr periods. Using a pulse and chase technique, with 125I and 131I c BSA in vitro and in vivo it was shown that newly phagocytosed antigen is found mainly in a lysosomal turnover compartment of a density 1.19 g cm–3. Antigen which has been in the cells for longer was found in a denser fraction (1.26 g cm–3). In a comparison of nhrmal and X-irradiated cells it can be shown that after irradiation with 900 r less c BSA is found in this storage compartment.

Binding of the antigen to the subcellular fractions, and its behavior towards several detergents has been studied. Subcellular fractions do not have the increased immunogenic capacity of antigen enclosed in living macrophages.

Two synthetic polypeptide antigens, poly(D-Tyr, D-Glu, D-Ala) and poly-(L-Tyr, L-Glu) have a different subcellular distribution from c BSA, BSA, or bovine gamma globulin. Apart from also being found in the 1.26 storage compartment the polypeptide antigens are mainly located in a 1.15 compartment and only to a small extent in the 1.19 compartment. The half-life of these antigens in the cells is much longer than the half-life of the protein antigens studied.

The finding of several subcellular compartments is discussed in connection with the functions possibly performed by macrophages.
THE EFFECT OF ANTIGENIC COMPETITION ON VARIOUS MANIFESTATIONS OF HUMORAL ANTIBODY FORMATION AND CELLULAR IMMUNITY
Authors: Eidinger David , Khan Salahuddin A. , Millar Kenneth G.
Published: June 2004

The effect of antigenic competition on various parameters of humoral antibody formation and cellular immunity was studied in mice.

Several pairs of antigens were employed in the investigation of the competitive aspects of induction of humoral antibody formation. Induction of a primary immune response to hemocyanin in Swiss white female mice moderately suppressed the induction of both 19S and 7S antibody formation to goose or rat erythrocytes. Suppression of 7S antibody formation was maximal when a time interval of 1–3 days separated the sequence of injections, although suppression was noted for intervals of up to 14 days. The induction of a primary immune response to rat RBC, the second of the two antigens in sequence, also suppressed The induction of both 19S and 7S antibody formation to goose RBC when appropriate intervals of 1–3 days were employed between injections.

The induction of a secondary immune response to rat RBC totally suppressed the primary induction of both 19S and 7S antibody formation to goose RBC administered in the appropriate time sequence. Subsequently, it was shown that the secondary immune response to the suppressed antigen (goose RBC) elicited 30 days after induction of a primary immune response (5 days after secondary immunization with rat RBC) was characterized by deficient 19S and 7S antibody production. These levels were suppressed even in comparison with a normal primary immune response to this antigen. The results were interpreted in part on the basis of a deficiency of formation of primed cells associated with immunological memory. Alternatively, evidence was obtained for the development of a split type of immunological tolerance in 6 of 10 animals studied, since a total suppression of 7S antibody production was obtained in association with deficient 19S antibody synthesis (titers < 1/10).

The induction of a primary immune response to several antigens in A/J female mice suppressed the processes of cellular immunity as manifested by prolonged survival of skin grafts from C57 BL/6J female donors.

These results were interpreted as evidence for the existence and utilization of processing cells by the initial immune stimulus yielding a deficiency of cells available for processing the second antigen administered in sequence.
THE EFFECT OF ACETYLSALICYLIC ACID ON PLATELET FUNCTION
Authors: Evans Geoffrey , Packham Marian A. , Nishizawa Edward E. , Mustard James F. , Murphy Edmund A.
Published: June 2004

Acetylsalicylic acid (ASA, aspirin) and sodium salicylate inhibit platelet aggregation induced by collagen, antigen-antibody complexes, gamma globulin-coated particles or thrombin. These compounds suppress the release of platelet constituents, such as adenosine diphosphate (ADP) and serotonin, induced by such stimuli. Since ASA and sodium salicylate do not inhibit ADP-induced platelet aggregation, it appears that their effect on the action of the other stimuli is due to a decrease in the amount of ADP released. The administration of ASA to rabbits (in doses which inhibited collagen-induced platelet aggregation) impaired hemostasis, prolonged platelet survival, and diminished the amount of deposit formed in an extracorporeal shunt.
THE LIFE CYCLE OF ANTIBODY-FORMING CELLS
Authors: Tannenberg Walter J. K. , Malaviya Anand N.
Published: June 2004

The generation, time of cells synthesizing 19S antibody was measured during the exponential phase of the primary and secondary immune responses. Using a plaque-forming cell assay together with a double label isotope method, the duration of the generation time was found to be about 13 hr, that of the S period was about 8 hr, and that of G-1 and G-2 were about 3 and 2 hr, respectively, in both immune responses.

Previous work was confirmed showing that all plaque-forming cells observed during the exponential phase of the immune responses incorporate labeled thymidine, and therefore take part in proliferation.

These results were obtained at points during both responses when the doubling time of the PFC was observed to be 6–7 hr. This finding makes untenable the hypothesis that the rate of appearance of PFC equals the rate of proliferation of these cells.

A hypothesis is presented to account for these findings and to serve as a basis for further experiments.
CYTOTOXICITY MEDIATED BY SOLUBLE ANTIGEN AND LYMPHOCYTES IN DELAYED HYPERSENSITIVITY
Authors: Ruddle Nancy H. , Waksman Byron H.
Published: June 2004

In the presence of specific antigen, lymph node cells from inbred rats with delayed hypersensitivity to tuberculoprotein, bovine gammaglobulin, and egg albumin produced progressive destruction of monolayers of rat embryo fibroblasts in tissue culture, first apparent at 48 hr and maximal at 72 hr. The effect was specific and did not depend on a genetic difference between the lymph node cells and target cells. It required antigen concentrations equal to or greater than 1.25 µg/ml and lymphocyte: target cell ratios of approximately 10 or 20:1. It could be evaluated both by a plaquing technique and by cell enumeration with an electronic particle counter.
CYTOTOXICITY MEDIATED BY SOLUBLE ANTIGEN AND LYMPHOCYTES IN DELAYED HYPERSENSITIVITY
Authors: Ruddle Nancy H. , Waksman Byron H.
Published: June 2004

Damage of rat embryo fibroblasts in the presence of sensitized lymph node cells reacting with specific antigen was shown to be closely correlated with delayed hypersensitivity in the animals from which the lymph node cells were taken. The phenomenon was not correlated with Arthus reactivity. In. animals sensitized with picryl conjugates of ovalbumin or human serum albumin, skin reactivity and the in vitro cytotoxic effect could be elicited only with the homologous conjugate or the protein carrier alone and not with picryl conjugates of heterologous proteins. Lewis rats developed more intense delayed sensitivity than BN rats, and Lewis lymph node cells were correspondingly more effective in producing specific damage of both syngeneic and allogeneic fibroblasts.
THE THYMUS AND RECOVERY OF THE SHEEP ERYTHROCYTE RESPONSE IN IRRADIATED MICE
Authors: Aisenberg Alan C. , Davis Caroline
Published: June 2004

The role of the thymus in the recovery of the sheep erythrocyte response after lethal irradiation has been studied in adult CBA mice with the hemolytic plaque technique of Jerne. This immunological parameter is markedly thymus-dependent. 10 wk after irradiation and after antigenic challenge the thymectomized animal has only one-twentieth to one-fortieth the number of plaque-forming cells as does the irradiated animal with intact thymus. The thymus continues to function into the 7th and 8th month of life in this strain. Unlike the drug-tolerant animal, the incompetent irradiated thymectomized mouse retains base line plaques (plaques without antigenic stimulation).

Thymectomy 18 days after irradiation is as effective as prior thymectomy in preventing recovery of the sheep cell response. Thymectomized animals receiving grafts of isogenic neonatal thymus (placed beneath the kidney capsule) 1 day, 1 wk, or 2 wk after irradiation are somewhat more responsive at 10 wk than intact animals. Grafts in place for 1 or 2 wk after irradiation and then removed result in one-fifth the recovery of grafts in place the entire time, while only slight restoration is obtained from grafts in place for the final 3 wk of the experiment. The results indicate that the thymus is not required for the 18 days after irradiation, that a period of at least 3 wk residence is required for complete restoration, and that the thymus itself is somewhat radiation-sensitive.

Allogeneic thymus grafts failed to restore the hemolysin response of irradiated thymectomized animals.
CAPSULATION OF PNEUMOCOCCUS WITH SOLUBLE C-LIKE (Cs) POLYSACCHARIDE
Authors: Bornstein Donald L. , Schiffman Gerald , Bernheimer Harriet P. , Austrian Robert
Published: June 2004

Capsulated mutants of pneumococcus producing a capsule of soluble polysaccharide related immunologically to the C or cell wall polysaccharide of pneumococcus have been isolated from several noncapsulated variants of this organism. The capsular material of these strains reacts with antisera both to homologous strains and to noncapsulated strains of pneumococcus and with human C-reactive protein. C-reactive protein has been shown to give a positive capsular precipitin or Quellung reaction with Cs pneumococcal variants and to agglutinate them.

The genetic locus which determines the production of Cs polysaccharide is situated in a region of the pneumococcal chromosome distinct from that controlling normal capsular polysaccharide synthesis. Binary and ternary capsulated pneumococci, one of the capsular components of which is Cs polysaccharide, have been isolated following DNA-mediated transformation.
IMMUNOCHEMICAL STUDIES ON THE SPECIFICITY OF CELLULAR HYPERSENSITIVITY
Authors: David John R. , Schlossman Stuart F.
Published: June 2004

The immunochemical specificity of antigen-induced inhibition of peritoneal exudate cell migration was studied in animals sensitized to chemically defined α,DNP(Lys)18 peptides. It was shown that sensitized peritoneal exudate cells could discriminate between various DNP-oligolysines. Only immunogenic members of the homologous series of α,DNP-L-lysines equal to or larger in size than the heptamer inhibited the migration of specifically sensitized peritoneal exudate cells. In contrast, nonimmunogenic α,DNP-L-lysines, a D-lysine containing stereoisomer of α,DNP L(Lys)9 (α,DNP-L4DL4) and (Lys)9ϵ, DNP were not inhibitory to the migration of peritoneal exudate cells derived from animals immunized to α,DNP(Lys)18.

The exquisite specificity of the in vitro reaction of sensitized cells with antigen contrasts with the previously observed in vivo or in vitro specificity of anti-α,-DNP(Lys)n antibody, but parallels the specificity of the in vivo delayed or anamnestic response. These results suggest the presence of a still undefined but highly specific binding site, which functions as the cellular receptor for antigen on the sensitized lymphoid cell or on some "processing" cell.
USE OF HYBRID ANTIBODY WITH ANTI-γG AND ANTI-FERRITIN SPECIFICITIES IN LOCATING CELL SURFACE ANTIGENS BY ELECTRON MICROSCOPY
Authors: Hämmerling Ulrich , Aoki Tadao , de Harven Etienne , Boyse Edward A. , Old Lloyd J.
Published: June 2004

Hybrid antibody [F(ab')2] with dual specificity for mouse γG and ferritin was prepared from the corresponding rabbit antisera, providing a precise reagent for locating mouse γG on cell surfaces. Viable cells were exposed successively to (a) mouse antibody to a cell surface antigen, (b) the rabbit hybrid antibody, and (c) ferritin, before preparation for electron microscopy. This method of

See PDF for Structure.

labeling is sensitive and specific and clearly lends itself to the introduction of visual markers other than ferritin. Other advantages are uniformity of labeling, ease of purification of the reagent, and circumvention of the many drawbacks arising from coupling ferritin to antibody chemically.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Gill D. Michael , Pappenheimer A. M. , Brown Robin , Kurnick James T.
Published: June 2004

When diphtheria toxin and NAD are added to soluble fractions containing aminoacyl transfer enzymes isolated from rabbit reticulocytes or from HeLa cells, free nicotinamide is released and, simultaneously, an inactive ADP ribose derivative of transferase II is formed. The reaction is reversible, and in the presence of excess nicotinamide, toxin catalyzes the restoration of aminoacyl transfer activity in intoxicated preparations. In living cultures of HeLa cells, the internal NAD concentration is sufficiently high to account for the rapid conversion, catalyzed by a few toxin molecules located in the cell membrane, of the entire cell content of free transferase II to its inactive ADP ribose derivative. Completely inactive ammonium sulfate fractions containing soluble proteins isolated from cells that have been exposed for several hours to excess toxin, can be reactivated to full aminoacyl transfer activity by addition of nicotinamide together with diphtheria toxin. Transferase II appears to be a highly specific substrate for the toxin-stimulated splitting of NAD and thus far no other protein acceptor for the ADP ribose moiety has been found.
RELATIVE INABILITY TO INDUCE TOLERANCE IN ADULT NZB AND NZB/NZW F1 MICE
Authors: Staples Parker J. , Talal Norman
Published: June 2004

Immunologic tolerance to ultracentrifuged bovine gamma globulin could not be induced in 6-wk old NZB or B/W mice, but developed readily in C3H, NZW, and C57Bl mice. NZB and B/W mice, as well as Balb/c mice, failed to become tolerant to ultracentrifuged human gamma globulin. The NZB and B/W mice also showed higher antibody titers to a standard antigenic challenge. This immunologic hyperreactivity and lack of experimental tolerance may be related to the lack of self-tolerance, autoimmunity, and lymphomas that develop in these mice at a later age.