bluuebunny/crossref_metadata_2025 huggingface dataset:
IDIOTYPE EXPRESSION AND THE INHERITANCE OF MOUSE ANTIBODY CLONES
Authors: Eichmann Klaus
Published: June 2004

The inheritance of idiotypes was investigated using idiotypic antisera against two monoclonal antibodies to streptococcal carbohydrates derived from A/J mice. Each of the two idiotypes was characterized by a special frequency of expression. One of the idiotypes was expressed in more than 80% of A/J mice, the other in less than 20%.

The idiotypes of both antibodies were strain specific and were transmitted to (A/J x BALB/cJ)F1 hybrid mice. Furthermore, both idiotypes remained associated with the A/J heavy chain C region allotype in (A/J x BALB/cJ)F1 hybrid mice. The results suggest that idiotypes are specified by allelic V genes, and that the heavy chain idiotype locus is linked to the heavy chain allotype locus.
AN IDIOTYPIC CROSS-REACTION BETWEEN ALLOTYPE a3 AND ALLOTYPE a NEGATIVE RABBIT ANTIBODIES TO STREPTOCOCCAL CARBOHYDRATE
Authors: Kindt Thomas J. , Klapper David G. , Waterfield Michael D.
Published: June 2004

Two antibodies to Group C streptococcal carbohydrate isolated from an individual rabbit had similar relative binding affinities for a Group C immuno-adsorbent column. Their light chains were similar, if not identical, as were the constant regions of their heavy chains. Differences in the variable regions of the H chains of the two antibodies were detected by chemical analysis. The two antibodies had serologically identical idiotypic determinants although one antibody possessed the a3 allotype and the other had no detectable group a marker. The occurrence of such antibodies indicates the absence of obligatory associations between group a allotypes and idiotypic specificities, despite the fact that both determinants have antigenic components in the VH region of the H chain.
SERUM-DEPENDENT PHAGOCYTOSIS OF PARAFFIN OIL EMULSIFIED WITH BACTERIAL LIPOPOLYSACCHARIDE
Authors: Stossel Thomas P. , Alper Chester A. , Rosen Fred S.
Published: June 2004

Paraffin oil containing oil red O and emulsified with lipopolysaccharide obtained from Escherichia coli was ingested rapidly by guinea pig polymorphonuclear leukocytes or human peripheral blood granulocytes and monocytes after opsonization by fresh homologous serum. The initial rate of engulfment of the particles was spectrophotometrically assayed by determination of cell-associated oil red O and reflected the opsonic activity of the serum. This activity was resistant to dialysis but labile to heat, hydrazine, and zymosan, required divalent cations, and was maximal in the presence of Ca++ and Mg++. It was associated with the fixation of [125I]C3 to the lipopolysaccharide particles. Genetically C3-deficient serum had no opsonic activity, and this activity was restored by the addition of purified C3. Normal and C4-deficient guinea pig serum and normal, C2-, and C4-deficient human sera were equally effective in opsonizing lipopolysaccharide particles and lipopolysaccharide particles sensitized with heat-inactivated lipopolysaccharide immune serum. Cord serum deficient in glycine-rich beta-glycoprotein (GBG) (properdin factor B) had diminished opsonic activity which was improved by addition of purified GBG. Thus, C3 fixation to lipopolysaccharide particles occurs by means of the properdin system, and the opsonization and ingestion of lipopolysaccharide particles constitutes a quantitative functional assay of this pathway.
REGULATION OF THE IMMUNE RESPONSE
Authors: Hoffmann Michael , Kappler John W.
Published: June 2004

The specificity of antigen recognition by thymus-derived helper cells (T cells) and antibody was examined in mice, heterologous erythrocyte antigens from sheep (SRBC), goat (GRBC), burro (BRBC), chicken (CRBC), and toad (TRBC) being used. Antibody specificity was tested by a number of functional assays: hemagglutination, hemolysis, and immune suppression. The specificity of T cells was determined by titrating their ability to help the in vitro antitrinitrophenol (TNP) responses of mouse spleen cultures immunized with the hapten coupled to the various test erythrocytes as carrier. Anti-SRBC antibody cross-reacted with GRBC, but not with BRBC, CRBC, or TRBC. In contrast, SRBC-primed helper T cells cross-reacted with both GRBC and BRBC, but not with CRBC or TRBC, indicating a difference in the specificity of antigen recognition between the cellular and the humoral immune responses.
LYMPHOCYTE TRANSFORMATION INDUCED BY AUTOLOGOUS CELLS
Authors: Weksler Marc E.
Published: June 2004

Lymphocytes incubated with phytohemagglutinin or concanavalin A develop the capacity to stimulate autologous lymphocyte transformation. This is not attributable to residual mitogen contaminating the lymphoblastic cell preparation as: (a) the dissociation of mitogen from the lymphoblastic cell preparation increases the degree of stimulation observed and (b) the kinetics of lymphocyte transformation stimulated by phytohemagglutinin-induced lymphoblasts is different from that stimulated by phytohemagglutinin. The appearance of the stimulatory determinants on lymphocytes exposed to phytohemagglutinin precedes morphological transformation.
THE RELATIONSHIP BETWEEN ß2-MICROGLOBULIN AND IMMUNOGLOBULIN IN CULTURED HUMAN LYMPHOID CELL LINES
Authors: Hütteroth T. H. , Cleve H. , Litwin S. D. , Poulik M. D.
Published: June 2004

ß2-microglobulin was detected on the cell surface and in the medium of human lymphoid cells established in long-term culture. The secretion of ß2-microglobulin was relatively uniform when different cell lines were compared, whereas IgG production varied widely. κ- and µ-membrane antigens were modulated by specific antibody; ß2-microglobulin was not modulated. Anti-κ and anti-µ antisera had no effect on the expression of membrane ß2-microglobulin, nor had anti-ß2-microglobulin antiserum any effect on the expression of κ- and µ-membrane antigens.
THE EFFECT OF BORDETELLA PERTUSSIS ON LYMPHOCYTE CYCLIC AMP METABOLISM
Authors: Parker Charles W. , Morse Stephen I.
Published: June 2004

Bordetella pertussis culture fractions produce decreased metabolic responses to isoproterenol and epinephrine in mice and rats, suggesting the possibility of systemic ß adrenergic blockade. The present study was undertaken to elucidate the mechanism of the alteration in adrenergic responsiveness and to clarify its relationship to other biological effects of the organism.

Lymphocytes were selected as a suitable tissue because of the marked alteration in lymphocyte distribution in pertussis-treated mice and rats, suggesting a change in the surface properties of these cells. Human peripheral blood lymphocytes, purified by nylon fiber chromatography, were studied. In short incubation experiments (20 min or less) B. pertussis did not alter the cyclic AMP response to isoproterenol, prostaglandin E (PGE1), or methacholine. However, when cells were preincubated with B. pertussis for 90 min at 37°C, the responses to all three agents were markedly inhibited.

Although these observations provide direct confirmation of the ability of B. pertussis to inhibit catecholamine responsiveness, the fact that PGE1 and methacholine responses were also inhibited suggests that blockade at the level of the ß adrenergic receptor is doubtful. The inhibitory activity was localized in a nondialyzable, protein-rich fraction that is precipitated from B. pertussis culture fluid by ammonium sulfate at 90% of saturation. The bulk of the activity was obtained in the load volume after 50,000 g centrifugation in a cesium chloride gradient, density 1.2–1.5 (fraction 4). Fraction 4 produced a change in lymphocyte hormonal responsiveness at concentrations as low as 5 ng/ml.

The relationship between cyclic AMP inhibitory activity in isolated human cells and leukocytosis-producing activity in intact mice was studied. The two activities seemed to parallel one another quite closely until the final Sephadex G-150 fractionation step, in which the two activities were obtained in the same column fraction, but a greater recovery of the leukocytosis-producing activity was obtained. Additional purification will be required to establish conclusively whether the same macromolecule is responsible for both activities.

The availability of a bacterial product that markedly inhibits cyclic AMP accumulation in purified lymphocytes may help to clarify the role of cyclic AMP in lymphocyte activation by antigen and nonspecific mitogens.
ACUTE DESTRUCTION BY HUMORAL ANTIBODY OF RAT SKIN GRAFTED TO MICE
Authors: Winn Henry J. , Baldamus Conrad A. , Jooste Somarie V. , Russell Paul S.
Published: June 2004

A study has been made of the roles played by complement and polymorphonuclear leukocytes (PMN) in the acute destruction of xenografts of rat skin that follows injection of their hosts with antisera specifically reactive with graft antigens. The rat skin was grafted onto mice whose immune responses were suppressed by removal of the thymus and a brief course of treatment with rabbit antimouse lymphocyte serum. At about 2 wk after grafting the mice were injected intravenously or intraperitoneally with mouse antirat serum (MARS). This time interval was chosen because it avoided the complications that might be associated with either the process of healing in or with incipient rejection. Signs of graft damage were evident as early as 10 min after the injection of MARS, and in most animals so injected the grafts were completely destroyed within 24–48 h.

The role of complement (C) in this acute destructive process is indicated by the results of three lines of experimentation. (a) Non-C-fixing antibodies or antibody fragments failed to cause damage to the grafts. Indeed, both chicken antirat serum and F(ab')2 fragments from rabbit antirat serum completely protected the grafts against the effects of MARS that was administered 24 h later. (b) When mice were depleted of hemolytic C by treatment with cobra venom factor or heat-aggregated gamma globulin, the damage caused by MARS was greatly reduced or completely inhibited. (c) In mice with a genetically determined absence of C5 much greater quantities of MARS were required to cause graft damage; the tempo of the destructive process was consistently slower; and a greater number of grafts recovered from the initial inflammatory process than was the case for animals with an intact complement system.

The participation of PMN in serum-mediated destruction of grafts was initially suggested by the results of microscope examination of fixed tissues. The essential role of these cells in the process is indicated by the failure of MARS to cause tissue damage in mice whose circulating PMN have been reduced to very low levels by treatment with nitrogen mustard or more specifically with an anti-PMN serum.

The absence of tissue damage when circulating PMN are reduced but C levels are normal suggests that C-mediated cytolysis is unimportant in graft destruction and that the role of C lies in its ability to generate chemotactic factors. The latter may then attract the PMN that provide mediators of tissue damage.
NATURE OF LYMPHOCYTE-TUMOR INTERACTION
Authors: Stulting R. Doyle , Berke Gideon
Published: June 2004

The binding of sensitized lymphocytes to tumor cells that leads to tumor cell lysis in vitro has been investigated using poly-L-lysine-fixed tumor cell monolayers and lymphocytes obtained from the anatomical site of tumor allograft rejection. The results show that magnesium is an important prerequisite for this interaction and that the extent of lymphocyte-tumor cell binding depends upon temperature as well as pH. Binding can occur in the absence of serum, although serum factors are necessary for the completion of the cytolytic process. The poly-L-lysine technique is applicable to the formation of confluent monolayers with virtually any normal or neoplastic cell type, including those that are otherwise nonadherent to surfaces. Cells immobilized by this technique can be used for the specific immunoabsorption and subsequent recovery of effector lymphocytes sensitized against transplantation or tumor cell antigens.
IDENTIFICATION OF A NOVEL CELL TYPE IN PERIPHERAL LYMPHOID ORGANS OF MICE
Authors: Steinman Ralph M. , Cohn Zanvil A.
Published: June 2004

A novel cell type has been identified in adherent cell populations prepared from mouse peripheral lymphoid organs (spleen, lymph node, Peyer's patch). Though present in small numbers (0.1–1.6% of the total nucleated cells) the cells have distinct morphological features. The nucleus is large, retractile, contorted in shape, and contains small nucleoli (usually two). The abundant cytoplasm is arranged in processes of varying length and width and contains many large spherical mitochondria. In the living state, the cells undergo characteristic movements, and unlike macrophages, do not appear to engage in active endocytosis. The term, dendritic cell, is proposed for this novel cell type.
SOME BIOCHEMICAL PROPERTIES OF THYMUS LEUKEMIA ANTIGENS SOLUBILIZED FROM CELL MEMBRANES BY PAPAIN DIGESTION
Authors: Muramatsu Takashi , Nathenson Stanley G. , Boyse Edward A. , Old Lloyd J.
Published: June 2004

Thymus leukemia (TL) alloantigenic activity was solubilized by papain proteolytic digestion from intact RADA1 tumor cells. If the cells were labeled with amino acids and fucose, the TL alloantigen could be isolated as a doubly labeled glycoprotein fragment by indirect precipitation from the papain digest. This TL glycoprotein fragment was approximately the same mol wt as the papain-digested H-2.4 alloantigen fragment as judged by chromatography on Sephadex G-150 in sodium dodecyl sulfate. The carbohydrate chain of the TL glycoprotein obtained by exhaustive pronase digestion behaved as a glycopeptide of approximately 4,500 mol wt, as compared with the glycopeptide of the H-2.4 alloantigen that had a mol wt of about 3,500. Thus, the TL alloantigen can be solubilized by papain digestion as a glycoprotein fragment similar in mol wt to the H-2 alloantigen glycoprotein fragment. The carbohydrate chain of the TL glycoprotein is larger than the H-2 carbohydrate chain.
REGULATION OF THE IMMUNE RESPONSE
Authors: Kappler John W. , Hoffmann Michael
Published: June 2004

The kinetics of the in vivo response to SRBC was studied in mouse spleen at both the B cell and T cell levels. The B cell response was assayed by following the appearance of antibody-secreting cells in the spleen using the hemolytic plaque assay. The T cell response was monitored by following the increase in or "priming" of helper activity in the spleen using a quantitative in vitro assay. The role of cellular proliferation in both responses was established with the inhibitor of mitosis, vinblastine.

The results show that, although the development of T cell activity precedes that of anti-SRBC PFC by as much as 1 day, T cells lag at least 1 day behind B cells in the onset of cellular proliferation.

The evidence suggests either that the helper T cell which proliferates in response to SRBC does so after helping in the initiation of the primary B cell response or that the proliferative T cell response and the initiation of the primary B cell response involve two different subpopulations of T cells.
ISOLATION AND IMMUNOCHEMICAL CHARACTERIZATION OF RABBIT 7S ANTI-IGG WITH RESTRICTED HETEROGENEITY
Authors: Bokisch Viktor A. , Chiao Jen Wei , Bernstein David
Published: June 2004

7S anti-IgGs were isolated from four rabbit antistreptococcal antisera by the use of immunoabsorbent columns. The isolated proteins were of restricted molecular heterogeneity; they formed a monodisperse band on microzone electrophoresis and had a limited number of light chain bands when analyzed on urea polyacrylamide gel. The binding site of the 7S anti-IgGs was detected in the F(ab')2 portion of the molecule. The binding site has antibody specificity for the Fc portion of IgG. For one 7S anti-IgG the combining site on the Fc portion could further be defined. A pepsin fragment of Fc, described as Pep-III', was a potent inhibitor of the coprecipitation of 7S anti-IgG with antigen-antibody complexes.

An idiotypic cross-reaction was detected between the 7S and 19S anti-IgGs isolated from the same rabbit with anti-idiotype sera prepared in guinea pigs. This idiotypic specificity was not detected in the 7S anti-IgGs of 20 other rabbits.
CHARACTERIZATION OF CYSTIC FIBROSIS FACTOR AND ITS INTERACTION WITH HUMAN IMMUNOGLOBULIN
Authors: Danes B. Shannon , Litwin Stephen D. , Hütteroth Thomas H. , Cleve Hartwig , Bearn Alexander G.
Published: June 2004

Cystic fibrosis factor activity (CFFA), assayed as the ability to stop oyster ciliary movement, was present in serum-free medium from actively growing cystic fibrosis skin fibroblast cultures. CFFA was associated with a low molecular weight, negatively charged molecule that contained no uronic acid and was heat and pH labile. When CFFA-positive media were mixed with human IgG1, the CFFA was chromatographically displaced and emerged with the IgG1 fraction on column chromatography. Experiments in which various immunoglobulins were added to CFFA-positive culture media and then incubated with specific anti-immunoglobulins suggested that CFFA binding was class specific for human IgG, subclass specific for IgG1 and IgG2, and occurred with intact unaggregated heavy chains but not with κ- and λ-light chains, or Fab, Fc, and F(ab')2 fragments. The serum protein ß2-microglobulin, which has structural homology to IgG, also bound CFFA.
ELECTRON MICROSCOPIC STUDIES ON STREPTOCOCCI
Authors: Swanson John , Gotschlich Emil C.
Published: June 2004

The location of Group A carbohydrate in the streptococcal cell wall has been studied by several ultrastructural techniques. The findings, based largely on use of ferritin- and horseradish peroxidase-conjugated antibodies, are interpreted as demonstrating a discrete laminar distribution of the group-specific polysaccharide. This carbohydrate layer is located on the outermost surface of the cell wall in organisms lacking protein cell wall antigens.
THE SYNTHESIS, ASSEMBLY, AND SECRETION OF GAMMA GLOBULIN BY MOUSE MYELOMA CELLS
Authors: Buxbaum J. , Scharff M. D.
Published: June 2004

The study of the synthesis, assembly, and secretion of IgM by seven murine myeloma tumors has revealed that free mu chain can be detected intracellularly after release from the ribosome. It combines with light chains to form µL. The major intracellular protein in six of the seven tumors was the 8S subunit. One tumor contained considerable amounts of 19S material intracellularly. Those tumors that did not contain 19S IgM intracellulariy appeared to assemble the subunits outside the cell.
PROLIFERATION OF B AND T CELLS IN MIXED LYMPHOCYTE CULTURES
Authors: Andersson Leif C. , Nordling Stig , Häyry Pekka
Published: June 2004

Electrophoretically fractionated CBA/Ca spleen T cells alone respond to allogeneic cells in one-way MLC and to PHA. They do not respond to E. coli LPS. B cells alone do not respond to allogeneic cells nor to PHA, but do respond to LPS. When karyotypically distinguishable syngeneic mixtures of T and B lymphocytes are stimulated with allogeneic cells, at the most 5% of mitoses on 5–9th culture day are of B cell origin. This indicates that B cells are not substantially recruited to proliferate in the MLC.
IODINATING ABILITY OF VARIOUS LEUKOCYTES AND THEIR BACTERICIDAL ACTIVITY
Authors: Simmons S. R. , Karnovsky M. L.
Published: June 2004

A rapid method that employs monolayers of different phagocytic cells, primarily from guinea pigs and mice, has allowed a kinetic determination of (a) ingestion by these cells of labeled particles, (b) fixation of 131I and (c) microbicidal activity in the cells after periods as short as 5' of exposure of bacteria to phagocytes. Phagocytes so examined included polymorphonuclear leukocytes (PMN) elicited into the peritoneal cavity, elicited peritoneal mononuclear cells (monocytes) (MN), and peritoneal macrophages (MAC) obtained simply by lavage. Circulating PMN from normal human subjects and from children afflicted with chronic granulomatous disease were also studied.

The potential for generation of H2O2 (a key component of the iodinating system) of all the normal cells studied, gauged by their content of cyanide-insensitive NADH oxidase, seemed comparable. Peroxidase levels varied widely, and were highest in PMN and almost undetectable in MAC. Catalase was at negligible levels in all the cell types obtained from mice. The fixation of 131I by phagocytes ingesting 14C-labeled dead tubercle bacilli appeared to be primarily a function of the cellular peroxidase content. Thus, mouse macrophages, with virtually no peroxidase, displayed no fixation of iodide. PMN proved far more able to fix 131I during phagocytosis than did MN. In experiments comparing PMN from normal human subjects and from children with chronic granulomatous disease (CGD), a sex-linked condition characterized by a deficiency of H2O2 production during phagocytosis and low microbicidal activity, the iodination ratio of CGD cells was dramatically less than that of normal PMN (by about two orders of magnitude). Capacity for iodination was correlated with bactericidal activity toward E. coli.

At low bacterial loads (ca. 5:1), phagocytes killed efficiently, and little discrepancy in ability among cell types was apparent. Under the stress of higher loads of 14C-labeled E. coli (ca. 100:1), differences in bactericidal activity were exaggerated, and a substantial disparity between MN and PMN was observed in favor of the latter. The hierarchy for killing efficiencies therefore agreed with that for iodination, with one notable exception: mouse MAC were consistently competent in their killing activity, more so than MN, even though they virtually lack peroxidase and the ability to iodinate ingested bacteria.
FUNCTIONAL HETEROGENEITY OF MURINE LYMPHOID CELLS
Authors: Stobo John D. , Rosenthal Alan S. , Paul William E.
Published: June 2004

An appreciable percent (3–14%) of the lymphocyte-like cells of the mouse spleen lack both the θ-isoantigen and sufficient surface immunoglobulin to be detected by conventional immunofluorescence or autoradiographic procedures. These θ-,Ig- cells are increased in frequency after treatment of mice with antithymocyte serum or in mice that have been thymectomized, irradiated (850 R), and reconstituted with bone marrow cells. Moreover, in chimeric C57BL/6 mice in which the T cells are derived from (BALB/c x C57BL/6)F1 donors, θ-,Ig- cells also lack BALB/c histocompatibility antigens. These experiments indicate that θ-,Ig- cells are not θ- T lymphocytes.

Removal of complement receptor lymphocytes from spleen cell populations increases the frequency of θ-,Ig- cells, indicating that such cells lack the complement receptor. Partially purified populations of θ-,Ig- cells have been obtained by cytolysis by anti-θ- and anti-κ-antibody and complement and by density gradient ultracentrifugation. These cells closely resemble lymphocytes in morphology. The only exceptional feature is the existence of prominent nucleoli. The θ-,Ig- cells lack hemoglobin and endogenous peroxidases, are not actively phagocytic, and do not adhere to glass. This suggests they are not of the erythroid, myeloid, or monocytoid lines. [3H]Thymidine labeling studies indicate that θ-,Ig- cells are members of a relatively slowly dividing cell pool. Whether θ-,Ig- cells are members of the "classical" B lymphocyte line or belong to another, as yet undescribed, lineage is not yet certain.
CELLULAR REQUIREMENTS FOR THE REJECTION OF SKIN ALLOGRAFTS IN RATS
Authors: Lubaroff David M.
Published: June 2004

The role of bone marrow-derived cells in the rejection of skin allografts in rats was investigated. Lewis rats, rendered tolerant of BN antigens and bearing healthy grafts, were thymectomized, irradiated with 900 rad, and injected with varying doses of either normal isologous bone marrow, normal lymph node cells, and/or lymph node cells presensitized to BN antigens. In some experiments rats were also adoptively sensitized to tuberculin. Results showed that, although necessary for the elicitation of tuberculin skin reactions, bone marrow cells are not needed for the rejection of previously tolerated skin allografts. Rats receiving lymph node cells alone rejected their grafts in about 6–7 days.

In addition, rats injected with bone marrow alone also rejected their grafts, although significantly later than did lymph node cell recipients, indicating that rat marrow contains a population of cells capable of reacting to transplantation antigens. These cells were found capable of reacting to major transplantation antigens but not minor as they were ineffective in causing the rejection of Ag-B compatible Fischer skin grafts. From experiments utilizing bone marrow from neonatally thymectomized donors and cells treated with an antiserum to rat T cells, these competent cells in the marrow were shown to be thymus derived.
ROLE OF HEPATIC ANION-BINDING PROTEIN IN BROMSULPHTHALEIN CONJUGATION
Authors: Kaplowitz N. , Percy-Robb I. W. , Javitt N. B.
Published: June 2004

Using gel filtration, the binding of both glutathione and Bromsulphthalein (BSP) to a liver-soluble protein was found to be identical. BSP-conjugating activity (glutathione S-aryltransferase) was present only in the fractions corresponding to the two protein-bound markers. Using a highly sensitive assay, with 3,4-dichloronitrobenzene, the pattern of glutathione S-aryltransferase activity was found to coincide with Y protein. This evidence suggests that Y protein, or ligandin, has a dual role in hepatic transport: a specific enzymic function in the conjugation of certain anions with glutathione in addition to a transport function in the intracellular binding of organic anions.
DETECTION OF IDIOTYPIC CROSS-REACTIONS AMONG STREPTOCOCCAL ANTISERA FROM RELATED RABBITS
Authors: Kindt Thomas J. , Seide Rochelle K. , Bokisch Viktor A. , Krause Richard M.
Published: June 2004

Idiotypic cross-reactions among antibodies to Group C streptococcal carbohydrate were studied using idiotypic antisera prepared in allotypically matched rabbits. Antibodies with idiotypic cross-specificity to one proband antibody were detected in 58% of the antisera from related rabbits, while approximately 1% of nonrelated rabbits produced antibody with this specificity. The cross-specificity was related to the group a (VH) allotype of 133 rabbits tested with only one exception.

Studies utilizing antisera against a second proband antibody failed to detect antibodies with idiotypic cross-reactivity among the same group of related rabbits. This result emphasizes the variation in expression of idiotypic determinants of antibodies.

It was further shown that the presence of anti-IgG's in the streptococcal antisera interfere with the detection of idiotypic cross-reactions. These anti-IgG's masked the presence of antibodies with idiotypic cross-specificity when inhibition of precipitation tests were used for their detection.
A RABBIT FAMILY OF RESTRICTED HIGH RESPONDERS TO THE STREPTOCOCCAL GROUP A-VARIANT POLYSACCHARIDE
Authors: Braun Dietmar G. , Kjems Ebbe , Cramer Matthias
Published: June 2004

Immunization of rabbits from a closed colony with streptococcal Group A-variant vaccines identified about two-thirds of them as low and heterogeneous responders. One-third of the rabbits showed a restriction of the response independent from the magnitude. Selective breeding from one monoclonal high-responder male and two restricted high-responder female rabbits succeeded in segregation of high-responder progeny after two generations. Their antibody levels were on the average 2.5 times higher than those of the random group of rabbits and a small group of low-responder offspring.

Immunization of 13 offspring originating from rabbits bred for restricted high response to the streptococcal Group C polysaccharide revealed that 11 progeny were restricted high responders and 2 progeny monoclonal high responders. This finding suggests that high responsiveness to the Groups A-variant and C polysaccharides is inherited as genetically linked traits.

Selective breeding combinations between restricted and monoclonal high-responder rabbits by brother-sister matings succeeded in narrowing the isoelectric focusing spectra of Group A-variant-specific antibodies in the offspring. It furthermore revealed a preferential expression of monoclonal antibodies after three generations with a similar net charge as those identified first in the original monoclonal paternal parent. These data suggest that similar copies of structural genes for the variable regions are transmitted from the parent to the progeny.
ROLE OF THE CLOTTING SYSTEM IN CELL-MEDIATED HYPERSENSITIVITY
Authors: Colvin Robert B. , Johnson Richard A. , Mihm Martin C. , Dvorak Harold F.
Published: June 2004

The expression of delayed-type hypersensitivity in animals has been inhibited by a variety of anticoagulants, but direct evidence for activation of clotting in the evolution of these reactions has been lacking. Using the fluorescent antibody technique we here demonstrate that fibrin deposition is a prominent and consistent feature of both allergic contact dermatitis and classic delayed hypersensitivity skin reactions in man. Fib was detected in 55 of 58 delayed reactions studied at the peak of their intensity. The characteristic distribution of Fib—principally in the intervascular portions of the reticular dermis with sparing of vessels and their associated cuffs of mononuclear cells—is unusual and quite different from that described in antibody-mediated lesions in animals or man. Fib was found in vessel walls in only 2 of 94 biopsies studied. With a single exception, deposition of immunoglobulins and complement was not observed.

The pathogensis and significance of Fib deposition in these reactions are not yet clear. Fib is ultimately derived from circulating fibrinogen, and its accumulation provides additional evidence for locally increased vascular permeability in delayed hypersensitivity. Polymerization of extravascular fibrinogen could be triggered nonspecifically by dermal elements (e.g., collagen) or by a product of sensitized lymphocytes. The appearance of Fib early in the development of these reactions (4–8 h after epicutaneous test with DNCB) and inhibition studies with anticoagulants together suggest that clotting may have a role in their pathogenesis, possibly by the release of bioactive peptides from fibrinogen/fibrin or by contributing to the induration characteristic of delayed hypersensitivity.
CELL INTERACTIONS BETWEEN HISTOINCOMPATIBLE T AND B LYMPHOCYTES
Authors: Katz David H. , Hamaoka Toshiyuki , Dorf Martin E. , Maurer Paul H. , Benacerraf Baruj
Published: June 2004

In the present study we have asked the question of whether F1 carrier-primed T cells can serve as helper cells for either or both parental B cells when (a) the carrier molecule employed is under genetic control such that one parental strain is a responder and the other is a nonresponder, and (b) the determinant specificity of the parental B cells being assessed is not under genetic control and bears no relationship to the specificity of the carrier molecule. Utilizing the system of immune response gene control of responses to the terpolymer L-glutamic acid-L-lysine-L-tyrosine (GLT) to which A strain mice (H-2a) are nonresponders, whereas BALB/c (H-2d) and (BALB/c x A)F1 hybrids (CAF1) are responders, these studies demonstrate that GLT-primed T cells of CAF1 donors can provide for responder BALB/c, but not for nonresponder A/J, the required stimulus for the anti-DNP responses of DNP-specific B cells of these respective parental strains to the DNP conjugate of GLT. The implications of these findings for Ir gene function in physiologic T-B cell interactions are discussed in detail.
INDUCTION OF A PRIMARY ANTIHAPTEN RESPONSE IN VIVO BY A GRAFT-VS.-HOST REACTION
Authors: Hamilton J. A. , Miller J. F. A. P.
Published: June 2004

A primary anti-NIP PFC response can be elicited by a GVH reaction provided certain structural requirements of the NIP-carrier are met. NIP-coated F1 erythrocytes and NIP-coated parental erythrocytes give rise to substantial anti-NIP PFC responses in F1 mice after the injection of parental spleens. These conjugates do not of themselves give rise to an anti-NIP PFC response and, in fact, normally give rise to NIP-specific tolerance. In contrast the GVH reaction is not able to enhance the primary anti-NIP PFC response to immunogenic NIP-conjugates.
THE ALLOGENEIC EFFECT IN INBRED MICE
Authors: Osborne David P. , Katz David H.
Published: June 2004

The studies presented herein were designed to directly evaluate the effects of a transient GVH reaction on T lymphocyte functions. To this end, we have shown that generation of carrier-specific helper cell function can be significantly influenced by the allogeneic effect. Thus, carrier-primed helper cells derived from CAF1 donor mice were generally much more active in specifically cooperating with syngeneic 2,4-dinitrophenyl (DNP)-primed B cells in adoptive recipients when parental A strain lymphocytes had been administered at some time during the priming regimen. This was true when allogeneic cells were administered concomitantly with the initial priming dose of carrier protein as well as when the GVH was induced in animals that had been exposed to antigen several days previously. This indicates that the allogeneic enhancing effects can be manifested on either primed or unprimed T cell populations. The ultimate effect of the GVH reaction on the development of helper T cell activity was found to be related to the number of allogeneic cells employed and the duration of the resultant GVH reaction in the carrier-primed host animal. Hence, allogeneic stimulation of slightly greater magnitude and/or longer duration resulted in marked suppression rather than enhancement of helper cell function in such donor mice. These findings may have general relevance to problems in autoimmune diseases and tumor immunity.
LYMPHOCYTE ACTIVATION IN SUBACUTE SCLEROSING PANENCEPHALITIS VIRUS AND CYTOMEGALOVIRUS INFECTIONS
Authors: Thurman G. B. , Ahmed A. , Strong D. M. , Knudsen R. C. , Grace W. R. , Sell K. W.
Published: June 2004

Efforts to stimulate lymphocytes from measles seropositive and two patients with subacute sclerosing panencephalitis (SSPE) with either commercially available measles virus or virus isolated from a known case of SSPE failed to show any significant data using a microculture assay. Similar results were obtained using lymphocytes from two patients with active cytomegalovirus (CMV) infections and CMV seropositive individuals using CMV suspensions.

On the other hand, lymphocytes from the patients with subacute sclerosing panencephalitis exhibited in vitro blastogenesis in culture with SSPE virus-infected HeLa cells. Similarly, lymphocytes from the CMV-infected patients demonstrated blastogenesis when cocultivated with CMV-infected WI-38 cells. This affords a new method for determining the cell-mediated immune capacity of patients with "slow" virus diseases.
EFFECT OF IMMUNOSUPPRESSION ON CHRONIC LCM VIRUS INFECTION OF MICE
Authors: Hoffsten Phillip E. , Dixon Frank J.
Published: June 2004

C3H mice chronically infected with LCM virus were found to be lethally affected by small doses of immunosuppression which caused bone marrow aplasia but had no effect on the amount of virus carried by the mouse. Humoral immune response of SWR/J mice to acute LCM infection was found to be totally suppressed by repeated single doses of 300 R/wk with no alteration in the level of virus carried by the mouse. In contrast, the established anti-LCM humoral immune response encountered in mice chronically infected with LCM virus was not suppressed by the same irradiation procedure. Over half of the chronic LCM carrier SWR/J mice treated with cyclophosphamide for 6 mo had total anti-LCM humoral immunosuppression, but showed no change in the level of virus carried. The glomerulonephritis which occurs in chronic LCM carrier mice was prevented by cyclophosphamide treatment in 90% of the mice. The humoral immune response which occurs in chronic LCM carrier mice appears to play no role in controlling the amount of virus carried by the mouse. Suppression of the LCM immune response by cyclophosphamide does prevent the development of glomerulonephritis in these mice.
PHYTOHEMAGGLUTININ MITOGENIC PROTEINS
Authors: Miller J. Bruce , Noyes Claudia , Heinrikson Robert , Kingdon Henry S. , Yachnin Stanley
Published: June 2004

The phytohemagglutinin (PHAP) glycoproteins derived from Phaseolus vulgaris consist of five isomitogens that are tetrameric structures made up of two different glycoprotein subunits. Although identical in size (mol wt = 34,000), the subunits differ in their isoelectric points and amino acid sequences for six of the first seven amino-terminal residues, but are identical in primary structure from the 8th through the 24th amino acid residue. The isomitogen containing four L subunits (L-PHAP) is a potent leukoagglutinin and mitogen that lacks hemagglutinating properties. The isomitogen made up of four R subunits (4R H-PHAP) is a potent hemagglutinin. The hybrid isomitogens consisting of varying proportions of the two subunits (3L-1R, 2L-2R, 1L-3R) are capable of causing mixed erythrocyte-lymphocyte agglutination. These studies provide a structural basis for explaining the differences in biological activities of the various PHAP isomitogens.
INDUCTION OF SKIN RESISTANCE TO VACCINIA VIRUS IN RABBITS BY VACCINIA-SOLUBLE EARLY ANTIGENS
Authors: Ueda Y. , Tagaya I.
Published: June 2004

The immunological role of vaccinia-soluble early antigen was examined in rabbits. The antigens were prepared from HeLa cells infected with a conditional lethal mutant of vaccinia virus, which induces in these cells early antigens including those responsible for surface immunofluorescence of infected cells, but not viral DNA and late protein syntheses. Immunization of rabbits with the antigens in Freund's complete adjuvant induced complement-fixing antibody but neither detectable circulating neutralizing antibody nor any detectable level of inhibitory substance or interferon in the skin of the animals. When immunized animals were inoculated intradermally with vaccinia virus, multiplication of virus in the skin was greatly inhibited, being accompanied by an earlier appearance as well as an accelerated wane of the local reactions. The resistance could not be transferred passively by the serum of immunized animals to normal rabbits. Immunization of rabbits with the antigens without the adjuvant not only failed to inhibit but, contrariwise, enhanced the multiplication of intradermally inoculated vaccinia virus, inducing heavy skin lesions and exalted virus multiplication.
REQUIREMENT FOR α-L-FUCOSE ON THE MACROPHAGE MEMBRANE RECEPTOR FOR MIF
Authors: Remold Heinz G.
Published: June 2004

α-L-fucose abolishes the activity of guinea pig migration inhibitory factor (MIF) on the macrophages. Other sugars such as α-D-glucose, ß-D-galactose, α-L-rhamnose, methyl-α-D-mannoside, and N-acetyl-ß-D-glucosamine had no effect. Theabolition of MIF activity by α-L-fucose was reversible. When macrophages were incubated with α-L-fucosidase, a glycosidase which splits terminal α-L-fucose from oligosaccharides, the macrophages no longer responded to MIF. On the other hand, MIF incubated with α-L-fucosidase was still active. These experiments strongly suggest that α-L-fucose comprises an essential part of a macrophage membrane receptor for MIF.
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO
Authors: Kapp Judith A. , Pierce Carl W. , Benacerraf Baruj
Published: June 2004

The cellular requirements for the development of primary IgG GAT-specific PFC responses in cultures of spleen cells from responder, C57Bl/6, mice stimulated with GAT and GAT-MBSA and in cultures of spleen cells from nonresponder, SJL and B10.S, mice stimulated with GAT-MBSA were investigated. Macrophages were required for development of responses to GAT and GAT-MBSA in cultures of spleen cells from responder mice and for responses to GAT-MBSA in cultures of spleen cells from nonresponder mice. Macrophages from nonresponder mice supported the development of responses to GAT by nonadherent responder spleen cells, indicating that the failure of nonresponder mice to respond to GAT is not due to a macrophage defect. Furthermore, responder macrophages supported the responses of nonadherent, nonresponder spleen cells to SRBC and GAT-MBSA, but not to GAT. This indicates that the capacity to respond to GAT is a function of the nonadherent population which is composed of thymus-derived (T) helper cells and precursors of antibody-producing cells. Treatment of spleen cells with anti-theta serum and complement before culture initiation abolished PFC responses to GAT and GAT-MBSA thus establishing the requirement for T cells in the development of PFC responses to these antigens.

Since precursors of antibody-producing cells in nonresponder mice are capable of synthesizing antibody specific for GAT after stimulation with GAT-MBSA and since the response to GAT is thymus-dependent, it appears that nonresponder mice lack GAT-specific helper T cell function.
GROUP A STREPTOCOCCAL BACTERIOCIN
Authors: Tagg John R. , Dajani Adnan S. , Wannamaker Lewis W. , Gray Ernest D.
Published: June 2004

A bacteriocin, streptocin A, was isolated from the supernatant fluid of tryptic soy broth cultures of Group A streptococcus strain FF-22. Evidence was obtained which supports the view that the failure to recover active streptocin A after growth of the producer strain in certain fluid media is due to the inactivation of the bacteriocin by concomitantly synthesized streptococcal proteinase.

The bacteriocin was purified 139-fold and the active product appeared to be of uniform size, having a molecular weight of approximately 8,000.

Streptocin A was bactericidal, but not lytic, for a susceptible Group A streptococcus and the lethal effect was markedly temperature dependent. The bacteriocin inhibited the synthesis of DNA, RNA, and protein, and also prevented the uptake and incorporation of glucose by the sensitive cells.

Degradation of RNA occurred, but appeared to be less than that produced by a staphylococcal bacteriocin. This effect may be due to differences in the killing potency of the two bacteriocins in preparations having similar inhibitory activity when measured by lawn culture assays.
INTERACTION OF HUMAN THYMUS-DERIVED AND NON-THYMUS-DERIVED LYMPHOCYTES IN VITRO
Authors: Geha Raif S. , Schneeberger Eveline , Rosen Fred S. , Merler Ezio
Published: June 2004

Relatively pure populations of human T and B lymphocytes were obtained from blood and tonsils using density gradient centrifugation in bovine serum albumin. Antigen alone was incapable of triggering the B lymphocyte into blast transformation or to secrete antibody. However, supernatants from tetanus toxoid-stimulated T cells obtained from immune donors contained a factor mitogenic for B lymphocytes. 50–60% of B cells responded to this lymphocyte mitogenic factor (LMF) by proliferation, loss of C3 reactivity, and change to a secretory state. LMF-stimulated B cells exhibited a three- to fivefold increase in protein secretion and a six- to eightfold increase in gamma G globulin secretion. De novo secreted IgG had specificity directed to the tetanus toxoid present in the LMF containing T-cell supernatants. This was confirmed by an increase in the number of indirect plaque-forming cells to tetanus toxoid-coated sheep red blood cells after stimulation of B cells with LMF. It is proposed that in the course of the response to a previously encountered protein antigen, sensitized human T cells emit a signal in the form of a soluble product that, together with antigen, triggers B cells into division and antibody secretion. The experimental model utilized can be adapted to study human T-B cell cooperation under various conditions in normal individuals and in individuals with immunodeficiency diseases.
A NEW SURFACE MARKER ON T LYMPHOCYTES OF HUMAN PERIPHERAL BLOOD
Authors: Hammarström Sten , Hellström Ulla , Perlmann Peter , Dillner Marie-Louis
Published: June 2004

Neuraminidase treatment of human peripheral blood lymphocytes uncovers cell surface receptors that bind purified A hemagglutinin from the snail Helix pomatia. No hemagglutinin was bound to untreated lymphocytes. Binding studies with 125I-labeled hemagglutinin suggested that the number of receptors on neuraminidase-treated lymphocytes was approximately 1·106/cell. The apparent association constant for hemagglutinin binding to lymphocytes, as calculated from Scatchard's plots, was 5–7·108 liters/mol.

Immunofluorescent staining with FITC-conjugated hemagglutinin gave positive reactions with approximately 60% of the lymphocytes from normal donors. Positive staining was inversely related to the number of lymphocytes with Fc or complement receptors or with surface immunoglobulin, thus suggesting that

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the lymphocytes with receptors for Helix pomatia A hemagglutinin are T cells. Cell fractionation on columns charged with hemagglutinin indicate that these receptors may be used for separating subpopulations of human peripheral lymphocytes.
OVERLAP STIMULATION OF PRIMARY AND SECONDARY B CELLS BY CROSS-REACTING DETERMINANTS
Authors: Klinman N. R. , Press J. L , Segal G. P.
Published: June 2004

Experiments were carried out to test the validity of the hypothesis that postulated differences in the nature of the antigen receptors of primary and secondary B cells should be reflected in a greater specificity in primary B-cell stimulation (2). Enumeration of clonal precursors stimulated by either DNP-Hy, TNP-Hy, or a mixture of both antigens confirmed this hypothesis. Since the sum of primary B cells stimulated by DNP-Hy and TNP-Hy is approximately equal to the number stimulated by a mixture of both, overlap stimulation of primary B cells by these antigens could be considered negligible. In contrast, the stimulation of B cells from mice previously immunized with DNP-Hy showed extensive overlap of stimulation by DNP-Hy and TNP-Hy. Thus secondary B cells appear less fastidious in their affinity requirements for stimulation than primary B cells.
MATURATION OF B LYMPHOCYTES IN THE RAT
Authors: Strober Samuel , Dilley Jeanette
Published: June 2004

The migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive anti-DNP response was studied. The adoptive primary response restored by unprimed spleen or thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) was markedly diminished as compared with that restored by unpassaged cells. On the other hand, the adoptive response restored by passaged spleen or thoracic duct cells from DNP-primed donors was greater than or the same as that restored with unpassaged cells, respectively. This suggests that unprimed B cells change from nonrecirculating to recirculating lymphocytes after exposure to antigen.

Studies of the adoptive anti-DNP response restored by unprimed or primed bone marrow cells showed little change in the time-course or amplitude of the response restored by either population of cells. The relative inability of marrow cells to carry immunological memory was related to the inability of recirculating memory cells to penetrate the marrow.

The turnover rate of unprimed and primed B cells was investigated by treating the cell donors with [3H]thymidine for 48 h before removal of thoracic duct or spleen cells. The adoptive anti-DNP response restored by unprimed or primed cells was not affected by [3H]thymidine treatment. This indicates that both populations of cells turn over slowly. However, our previous studies show that unprimed B cells involved in the adoptive antibody response to ferritin turn over rapidly. The different findings are discussed in the context of antigen-dependent B-cell maturation.