bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenicity of macrophage‐bound antigens: the requirement for hapten and carrier determinants to be on the same molecule for t and b lymphocyte collaboration
Authors: Unanue E. R. , Katz D. H.
Published: February 2007

The hapten‐protein conjugate, 2,4‐dinitrophenyl‐hemocyanin [DNP‐KLH], is highly immunogenic when bound to macrophages of normal mice. Indeed, such macrophages effectively stimulate a strong anti‐hapten response if presented to lymphocytes from mice previously immunized to the same hapten protein conjugate. On the other hand, the lymphocytes will not respond if the macrophage contains the hapten bound to an unrelated carrier, such as bovine IgG. In these experiments we tested whether such lymphocytes would respond immunologically to the hapten and carrier determinants, if these were in different molecules, but presented on the same macrophage. We have found that lymphocytes from DNP‐KLH immune mice respond weakly to macrophages that contain both the hapten DNP on bovine IgG plus hemocyanin. Hence, the optimal T and B lymphocyte collaboration via macrophages demands that both the haptenic and carrier determinants be on the same molecule.
Cellular and humoral immune responses in guinea pigs and rabbits to chemically defined synthetic peptides
Authors: Kelly Barbara , Levy Julia Gerwing , Hull D.
Published: February 2007

Two peptides shown previously (Biochemistry 1971. 10: 1763) to constitute the two major antigenic determinants of performic acid‐oxidized ferredoxin (O‐Fd) from Clostridium pasteurianum were studied in terms of their immunological properties. These peptides, designated the “N” (the NH2‐terminal heptapeptide of O‐Fd) and the “C” (the COOH‐terminal pentapeptide of O‐Fd) haptens, were synthesized and linked together in various ways to obtain peptides of a comparable length. The following peptides were prepared and used in this study: N‐10‐C, containing the N and C haptens linked by ten glycine residues, N‐8‐N, containing two N haptens linked by eight glycine residues and C‐mal‐10, constituting a symmetrical molecule with two C haptens each with a free COOH‐terminal and bridged by a malonic acid and ten glycine residues. All of these peptides were immunogenic in that they elicited both immediate and delayed skin reactions in immunized guinea pigs and stimulated increased uptake of [3H]thymidine in lymphocytes from appropriately sensitized animals. The peptides N‐10‐C and N‐8‐N also elicited the production of circulating antibodies in immunized rabbits. No antibodies to C‐mal‐10‐C were detected by the methods used here. Lymphocytes taken from guinea pigs sensitized to N‐10‐C were stimulated when they were cultured in the presence of either a conjugate of poly‐D‐glutamic acid and the C hapten (ratio of 1:22) or poly‐D‐glutamic and the N hapten (ratio of 1:18), indicating that the response was directed to the haptenic groups alone and not to the bridge structure. Lymphocytes from animals sensitized with C‐mal‐10‐C were not stimulated by N‐10‐C and appeared to require the presence of at least two C haptens per molecule before cell transformation could be elicited. On the other hand, lymphocytes from animals sensitized to N‐8‐N were stimulated with N‐10‐C, but not with the N hapten alone, indicating that while only one haptenic group was essential for stimulation, it had to be presented to reactive cells in a form other than as the free hapten. The implications of the results are discussed.
Mesenteric lymph as a major source of serum IgA in guinea pigs and rats
Authors: Vaerman J. P. , André C. , Bazin H. , Heremans J. F.
Published: February 2007

The mean concentration of IgA in the mesenteric lymph of guinea pigs and rats was 4.5 and 13.4‐fold higher, respectively, than that in their serum. For IgG, IgM, albumin, transferrin and α‐macroglobulin, the mesenteric lymph‐versus‐serum concentration ratios were lower than unity and inversely related to their molecular size, indicating that their presence in mesenteric lymph was essentially due to filtration through the walls of the mesenteric blood capillaries. In contrast, it was calculated that 90–97 % of IgA in mesenteric lymph was derived from local synthesis by the intestinal immunocytes. Considering mesenteric lymph flow and plasma volume, it was concluded that the intestinal mucosa is a major source of serum IgA in guinea pigs and rats.
Bursal and postbursal stem cells in chicken. functional characteristics
Authors: Toivanen P. , Toivanen A.
Published: February 2007

Cyclophosphamide (CY)‐treated or surgically bursectomized, CY‐treated 3‐day old chicks were injected with bursa or bone marrow cells from donors of different ages. Cell recipients and donors were isogeneic at the major histocompatibility locus. Antibody responses to sheep red blood cells and Brucella abortus, and microscopic morphology of spleen and bursa were assessed 5–6 weeks after the cell transplantation. Relative weight of the bursa was found to be a reliable indicator of the restoration of bursal structure. The results indicate that stem cells or progenitor cells for the B cell line in chicken can be divided into a bursal stem cell and a postbursal stem cell. Both of these cell types are effective in restoring antibody formation of CY‐treated chickens.

Bursal stem cells restore the bursal morphology; they are not capable of further maturation without the influence of the bursal microenvironment. This influence is not effected by bursa in a cell impermeable diffusion chamber; actual contact with the bursal stroma is necessary. Bursal stem cells are also capable of restoring the formation of germinal centers in the spleen of CY‐treated chickens. Postbursal stem cells do not restore bursal structure and they do not need the bursal micro‐environment for further maturation. They also have no clear effect on the formation of germinal centers in the spleen. Bursal stem cells are found in the bursa during the first few weeks after hatching. Postbursal stem cells start to appear in the involuting bursa and at the same time, in the bone marrow also. They are found as the majority of cells in the bursa and bone marrow after at least the 10th week following hatching. Early postbursal stem cells have already passed the education given by the bursa, but have not yet totally lost their capacity to induce germinal centers in the spleen. They restore germinal center formation even in surgically bursectomized recipients, demonstrating that presence of bursal follicles is not necessary for the production of germinal centers.

The findings are discussed to stress the significance of two equally important factors in the development of immunity: the lymphoid cells themselves and, at each stage ontogeny, the proper microenvironment for their further function and maturation.
Mendelian segregation of a mouse antibody idiotype
Authors: Eichmann K. , Berek Claudia
Published: February 2007

The expression of a mouse antibody idiotype (A5A) was found to be controlled by a gene in the heavy chain linkage group. The segregation of this idiotype in backcross experiments followed the segregation of the heavy chain allotype. A single backcross mouse had a recombinant phenotype.
Growth hormone‐induced t cell differentiation
Authors: Arrenbrecht S. , Sorkin E.
Published: February 2007

Lymphoid cell suspensions were transferred into normal or thymectomized suckling mice and the recipients treated with growth hormone. After immunization, the number of antibody‐forming cells was counted in the spleens of recipients.

Growth hormone was able to enhance the helper function of normal thymocytes, but not of lymph node and spleen cells or hydrocortisone‐resistant thymocytes.

It is concluded that growth hormone induces T‐cell characteristics in thymocytes.
Detection of t and b cell‐specific heteroantigens on electrophoretically separated lymphocytes of the mouse
Authors: Zeiller K. , Pascher G.
Published: February 2007

Mouse spleen lymphocytes were electrophoretically separated into pools of T and B lymphocytes. Heteroantisera were raised in rabbits against these cell pools, the IgG fractions were isolated and their lymphocytotoxicity tested. After appropriate absorption, the antisera were specifically directed against lymphocyte antigens. Further cross‐absorption with T and B lymphocytes made the antisera specific for antigens which were mutually exclusively present on T and B cells and were related to neither alloantigens nor immuno‐globulins. These anti‐B and anti‐T cell antisera killed antibody‐forming cells and graft‐versus‐host reactive cells, respectively, in vitro. Furthermore, anti‐B cell antiserum was cytotoxic to lymphocytes of low electrophoretic mobility in bone marrow and peripheral organs, except in the thymus, whereas anti‐T cell antiserum was cytotoxic to lymphocytes of high electrophoretic mobility in all organs and, in addition, killed all thymocytes of low electrophoretic mobility, which had not been affected by anti‐B cell antiserum. This distribution of lymphocytes in the electrophoretic distribution profiles, together with the described properties, gives evidence that heteroantigens were found to be exclusively present on T and B cells. They were designated “mouse B cell‐specific” and “mouse T cell‐specific” antigens and are part of mouse lymphocyte‐specific antigen.
T lymphocyte specificity of a lymphocyte‐inhibiting factor (chalone) extracted from the thymus
Authors: Florentin Irène , Kiger Nicole , Mathé G.
Published: February 2007

The lymphocyte‐inhibiting factor extracted from the thymus (LIFT) is effective in decreasing several immune responses. The aim of this study was to determine whether LIFT is able to depress humoral immune reactions and if so, whether it acts on T lymphocytes, B lymphocytes, or both.

Simultaneous administration of LIFT and antigen severely impairs the IgG antibody formation against dinitrophenylated human IgG (DNP‐HGG(a highly T lymphocyte‐dependent response) and, to a lesser extent, the IgM antibody formation against sheep red blood cells (a partly T lymphocyte‐dependent response). In contrast, the IgM anti‐DNP‐polymerized flagellin response (which does not require T lymphocyte collaboration) is not depressed at all by such treatment. These results demonstrate a LIFT action specificity on T lymphocytes only, and strongly argue for the assimilation of LIFT with a T lymphocyte chalone. The existence of a lymphocyte‐inhibiting factor specific for B lymphocytes, or B lymphocyte chalone, is discussed.
Assays for cellular antigens in the presence of detergents
Authors: Williams A. F.
Published: February 2007

When red blood cells or lymphocytes were fixed with glutaraldehyde, binding assays for determinants recognized by antibodies could be carried out in the presence of nonionic detergents. Specific inhibition of the binding assays by detergent‐solubilized membranes and cell extracts was possible, thus allowing rapid routine assays of detergent extracts during the purification of membrane components. The assay system was established for rat histocompatibility antigens and for cell‐associated immunoglobulin.
Homogeneity of antibodies produced by clonesin vitro
Authors: Luzzati Alma L. , Lefkovits I. , Pernis B.
Published: February 2007

Peripheral blood lymphocytes from primed rabbits were stimulated with sheep red cells (SRC) in microcultures. In this method, if a limiting number of lymphoid cells is used, only a small percentage of the cultures responds with production of antibody.

We have analyzed the antibody produced in the responding cultures from the point of view of allotype and electrophoretic mobility. In rabbits heterozygous at the b locus, the anti‐SRC antibody in single cultures was shown to express either one or the other allele. In a few of the cultures the antibody produced did not express any b locus allotype and was therefore assumed to be carrying lambda‐type L‐chains.

In high voltage agar electrophoresis, the antibody activity of most of the positive cultures was localized in a single band, the position of which varied from culture to culture.

These results show that the antibody produced in single microcultures is the product of single B cell clones. The homogeneity for allotype observed in the antibody produced by single microcultures is strong evidence that allelic exclusion, once achieved, is maintained throughout clonal proliferation.
Quantitative effect of mycobacteria and of anaerobic corynebacteria upon immunogenic activity of azobenzearsonate‐n‐acetyl‐l‐tyrosine in guinea pigs
Authors: Degrand Françoise , Raynaud M.
Published: February 2007

The adjuvant effect of Mycobacteria or Corynebacterium granulosum for inducing delayed‐type hypersensitivity to azobenzenearsonate‐N‐acetyl‐L‐tyrosine was investigated. A linear dose‐effect relationship was demonstrated.
Development of rough endoplasmic reticulum in mouse splenic lymphocytes stimulated by mitogens
Authors: Shohat Maya , Janossy G. , Dourmashkin R. R.
Published: February 2007

The development of rough endoplasmic reticulum (RER) was studied in mouse spleen cell cultures stimulated by lipopolysaccharide (LPS), a B lymphocyte mitogen, and in cultures stimulated by concanavalin A (Con A) which preferentially stimulates T lymphocytes. After 16–28 h incubation with LPS, stimulated B cells became large lymphoblasts with copious cytoplasm filled with polyribosomes. From 28 h onward, the membrane elements (ER) of RER started to develop from the existing channels of RER around the mitochondria, and polyribosomes became attached to the ER. The expanding RER gradually occupied larger parts of the cytoplasm and after 4½ days' stimulation with LPS, typical plasma cells could be found.

In Con A‐stimulated cultures, large lymphoblasts developed and after 4½ days, mainly intermediate‐sized cells could be recovered with cytoplasm containing mostly single ribosomes and virtually no RER. No direct morphological evidence has been found for “contagious” B cell activation by T cell mitogens such as Con A.
Spécificité antigénique individuelle de protéines de myélomes murins
Authors: Kolb J. P. , Lespinats Et Geneviève
Published: February 2007

Five murine BALB/c myeloma proteins have been studied for their antigenic specificities: IgG1, IgG2 and three of the IgA class. In each case we could demonstrate individual antigenicity and elicit monospecific antibodies for each protein.

Using the passive hemagglutination of sheep red blood cells coated with protein by the monospecific homologous antiserum, and its inhibition by normal immunoglobulins, we tried to determine whether a normal immunoglobulin population of syngeneic mice could exhibit the counterpart of these individual antigenic specificities.

The specific counterparts of proteins IgG1 and IgG2 have been found; the quantities of both normal immunoglobulins and of paraproteins needed to ensure the same inhibition of the antiserum were at a ratio of about 1000 : 1.

However, we were unable to detect such a counterpart for the three IgA myeloma proteins, although we observed a reaction of antigenic identity between two IgA proteins.
Carrier inhibition in the in vitro response to a hapten‐erythrocyte conjugate
Authors: Schwarze G. , Pünter J.
Published: February 2007

The in vitro induction of 4‐hydroxy‐5‐iodo‐3‐nitrophenacetyl (NIP)‐specific plaque‐forming cells by NIP‐SRC (sheep red blood cells) can be specifically inhibited by the presence of free SRC in the cultures, but only when low doses of hapten‐erythrocyte conjugate and of free SRC are used. At high concentrations of free SRC, the NIP response is specifically enhanced. Thus, only at low antigen concentrations can the in vitro system be seen as a model of physiological T‐B interactions.
Thymus‐dependent cytotoxic lymphocytes in the rat
Authors: Hersey P.
Published: February 2007

The nature of effector cells mediating cytotoxicity in vitro in a rat tumor allograft model using 51Cr release assays has been investigated. On the basis of a series of in vitro cell depletion techniques including glass absorption, removal of Fc receptor‐bearing cells and lysis of thymus‐dependent lymphocytes with a cytotoxic rabbit anti‐thymus cell sera, the predominant effector cell in this situation appears to be a thymus‐dependent lymphocyte. The main difference from previous published studies in mice appears to be the more rapid evolution of cytotoxic activity in the rat and the difficulty in detecting marked cytotoxic activity in the thoracic duct cells. Determination of the antigenic specificity of these cytotoxic cells by an inhibition assay suggests that their specificity is directed solely to transplantation antigens on the tumor cell.
Characterization of an immune response gene in rats
Authors: Würzburg U. , Schütt‐Gerowitt Heidi , Rajewsky K.
Published: February 2007

Responsiveness to porcine LDHA (a lactic dehydrogenase isoenzyme) in rats is controlled by a dominant gene, Ir‐LDHA, which is linked to the major histocompatibility locus. This gene is unlinked to the gene coding for an allotypic marker on the major class of rat immunoglobulin light chains.

Ir‐LDHA controls a specific step in the immune response to the enzyme molecule. The specificity of this step can not be ascribed alone (if at all) to the overall charge of the antigen.

High responder lymphocytes retain high responsiveness in a low responder environment. In addition, low responder animals do not appear to contain a material that cross‐reacts with rat anti‐LDHA antibody and that is not present in high responder animals.

High, but not low responder lymph node cells could be stimulated by antigen into proliferation in vitro. Low responder animals showed deficiency in developing LDHA‐specific helper function. These data suggest that Ir‐LDHA is expressed at the level of T cell function.
Studies on thymus products. VI. The effects of cyclic nucleotides and prostaglandins on rosette‐forming cells. Interactions with thymic factor
Authors: Bach Marie‐Anne , Bach J.‐F.
Published: February 2007

Cyclic AMP, its dibutyryl derivative and prostaglandins, PGE1 and PGE2, do not modify the numbers of rosette‐forming cells (RFC), but they do alter these cells' sensitivity to in vitro inhibition by azathioprine (AZ) and anti‐theta serum (ATS). In thymectomized mice, cyclic nucleotides and prostaglandins mimic the action of the thymic factor contained in thymic extracts and in normal serum, correcting the low spleen RFC sensitivity to AZ and ATS induced by thymectomy. Moreover, the mixture of infraliminal active doses of cyclic AMP and of thymic extracts (or normal mouse serum) also gives this effect. In normal mice, the nucleotides (but not prostaglandins) lower the AZ and ATS sensitivity of RFC, which remains insensitive to thymic extracts. Theophylline and isoproterenol have effects similar to those of cyclic AMP, a result in accord with their postulated interactions with the adenyl‐cyclase system. Noncyclic AMP and cyclic GMP show no effect in the RFC assay system at doses 10–100 times higher than active doses of cyclic AMP. Other vasoactive compounds, including epinephrine, phentolamine, propanolol, and angiotensin, do not show any effect on RFC.
Analysis of anti‐hapten foci in repopulated mouse spleens
Authors: North J. R. , Feinstein A.
Published: February 2007

We have demonstrated by two separate techniques the formation in vivo of foci of anti‐(4‐hydroxy‐3‐iodo‐5‐nitrophenyl)acetyl (NIP) antibodyforming cells. The initiation and expansion of such foci in the spleens of irradiated mice has been shown to depend on the presence of both hapten‐and carrier‐primed spleen cell populations.

Sensitive methods have been developed to assay the heterogeneity of antibody produced in single anti‐hapten foci, usually of less than 1000 plaque‐forming cells. Foci from NIP‐BSA (bovine serum albumin)‐primed spleen cell inocula have been shown to be usually monoclonal. Using mixtures of BSA‐primed and NIP‐ovalbumin primed spleen cells, the effect of changing the ratio of cooperating cell types upon the homogeneity of antibody in foci has been studied. The results are interpreted as preliminary evidence in favor of a high degree of B cell selection operating during focus initiation.

An effect of carrier‐primed cell numbers on the size of anti‐hapten foci has been detected and some morphological features of foci are described.
Fractionation of cytotoxic T lymphoblasts on Ficoll gradients by velocity sedimentation
Authors: Greenberg A. H.
Published: February 2007

Velocity sedimentation of lymphoid cells on linear Ficoll gradients in polycarbonate tubes provides a simple reproducible technique for fractionating lymphocytes from lymphoblasts. Using this method the T lymphoblast was characterized as an important cytotoxic cell in the early immune response to the H‐2d alloantigen of the P‐815‐Y mastocytoma, and at a later time the small lymphocyte was shown to be the predominant cytotoxic cell. Enrichment and depletion of cytotoxic lymphocytes was also demonstrated in fractionated spleens.
Carrier function of the polypeptides (T,G)‐A–L and (H,G)‐A–L in high and low responder mice
Authors: Wrede J. , Rüde E. , Thumb Renate , Meyer‐Delius Margot
Published: February 2007

The immune response of mice to the synthetic polypeptides (T,G)‐A–L and (H,G)‐A–L is genetically controlled by the Ir‐1 locus. In an attempt to characterize the cell type(s) involved in this control, DNP‐conjugates of (T,G)‐A–L and (H,G)‐A–L were used to study the carrier function of these polypeptides. In adoptive cell transfer experiments carried out in C57BL and C3H mice it was found that in contrast to the respective high responder strain, low responder mice appear to be incapable of recognizing these polypeptides as carriers. This is compatible with the hypothesis that low responders are defective with respect to the specific stimulation of thymus‐dependent lymphocytes by (T,G)‐A–L or (H,G)‐A–L, or to the cooperation of these cells with the precursors of antibody‐producing cells.
Comparison of the suppressive effect of thymus cells and the suppression by neonatal application of antigen
Authors: Droege W.
Published: February 2007

The suppressive effect of thymus cells on the agglutinating antibody response in chickens is shown to be antigen‐specific. Experiments reveal that this effect can be seen several weeks after thymus cell transfer, if the respective antigen (A) is given 3 times weekly after transfer. Repeatedly applied high doses of the antigen (A) result in a stronger effect than low antigen doses, and mercaptoethanol‐resistant antibody (IgG) is usually more affected than the total titer (of which IgM is the major contributor). Finally, several weeks after thymus cell transfer, when the response to antigen A is still lower than that of the normal controls, the antibody response to an unrelated antigen B is normal. By these three criteria, as well as by the degree of suppression, the suppressive effect of thymus cells strikingly resembles the phenomenon of antigen‐specific suppression that is seen after antigenic stimulus in the prenatal or early postnatal period.

The suppressive effect is already given by thymus cells from 10‐day old donors. As in previous studies, the suppressive activity was significantly diminished in thymus cells from neonatally bursectomized donors. The data indicate that a specifically acting suppressor cell compartment exists which is different from B cells and cooperative or graft‐vs‐host‐active T cells.

The results are discussed in light of current concepts of “self‐tolerance”.
Cellular composition of the chicken thymus; effects of neonatal bursectomy and hydrocortisone treatment
Authors: Zucker R. , Jauker Uta , Droege W.
Published: February 2007

The cellular composition of the young chicken thymus has been analyzed by using 3 different physical parameters: cell volume, electrophoretic mobility, and the buoyant density of the cells. The analyses revealed the presence of 3 major subpopulations in the thymus of 16‐week old chickens. These populations comprised about 66%, 19% and 15% of the thymic lymphoid pool. The data indicate that the last population, representing 15%, predominates in the medulla and is competent for GvH reactions.

Marked effects on the cellular composition of the young chicken thymus are observed after neonatal bursectomy or after hydrocortisone treatment. Several findings suggest that the effect of bursectomy is not to be explained by B cell contamination in the chicken thymus. The data indicate the existence in the young chicken thymus of a bursa‐dependent cellular subpopulation different from peripheral B lymphocytes but also different from cooperative or GvH active T cells. This subpopulation represents a part of the 66% small cells, and is estimated to constitute about 15% of the thymic lymphocyte pool.
The susceptibility of the mouse immunoglobulin subclasses to suppression by high doses of antigen
Authors: Hay F. C. , Torrigiani G.
Published: February 2007

Using the coprecipitation technique and rabbit antisera specific for mouse IgG1, IgG2a, IgG2b, IgA and IgM, the responses of BALB/c mice to a wide range of doses of human serum albumin have been studied. Antibody activity was detected in all five classes. At lower doses, below 1 mg, the distribution of antibody activity among the immunoglobulin classes was fairly constant, but at higher doses a decrease in antibody activity occurred in certain subclasses only, particularly IgG1. The actual effect obtained depended on whether the antigen was given with or without Bordetella pertussis. To study the subclass suppression further, mice were also subjected to neonatal treatment with soluble antigen. The suppression here was again mainly in the thymus‐dependent IgG1 subclass.
Suppression of immunological memory for a cross‐reactive idiotype in adult mice
Authors: Pawlak L. L. , Hart D. A. , Nisonoff A.
Published: February 2007

Previous investigations have demonstrated the feasibility of suppressing the production of an idiotype, associated with anti‐p‐azophenylarsonate antibodies in A/J mice, by pretreatment of adult mice with anti‐idiotypic antiserum. The present study indicates that immunological memory, with respect to the formation of the cross‐reactive idiotype, can similarly be suppressed in adult mice by intraperitoneal inoculation of rabbit anti‐idiotypic antiserum. There was no concomitant suppression of the formation of anti‐hapten antibody lacking the cross‐reactive idiotype, nor of antibody to the protein carrier. The data indicate that the immunoglobulin receptors present on memory cells are available to the injected anti‐idiotypic antibodies and that these cells are not sequestered. The data do not distinguish between inactivation or destruction of memory cells in vivo.
The mechanism of bone marrow‐derived (B) lymphocyte activation. I. Early events in antigen‐induced triggering in the presence of polymerized flagellin
Authors: Schrader J. W.
Published: February 2007

The primary in vitro response to fowl IgG (FGG) of spleen cells from congenitally athymic (nu/nu) mice was used as a model of antigen‐induced bone marrow‐derived (B) lymphocyte activation. Functional evidence was presented that deaggregated FGG (De‐FGG) bound rapidly to B lymphocytes at 0 °C, an antibody‐forming cell (AFC) response to FGG occurring if the spleen cells, after washing off of unbound FGG, were subsequently cultured in the presence of polymerized flagellin (POL). This supported the concept that antigen can induce B cell triggering without being presented in a multivalent form.

Conversely, De‐FGG could not be demonstrated by functional studies to bind to spleen cell suspensions at 37 °C so as to initiate subsequent triggering in the presence of POL. In fact, FGG which had bound at 0 °C became ineffective in B cell triggering if the spleen cells were briefly incubated at 37 °C before being washed and cultured with POL. However, if cells were incubated for 60 min at 37 °C with FGG in the presence of POL, washing of the cells did not prevent a significant response in the absence of further additions of FGG. When cells that had been incubated for 60 min at 37 °C with FGG and POL were treated with trypsin and were cultured without the addition of further POL or FGG, a significant anti‐FGG antibody‐forming cell response still occurred. This implied that activation of some B cells had proceeded within 60 min to a stage independent of further extracellular antigen. It was shown that this initial activation proceeded independent of the presence of fetal calf serum.

An additional observation was that when cells that had been incubated at 37 °C with FGG plus POL were treated with trypsin after they had been washed, the subsequent anti‐FGG response was reduced compared to that of cells that had merely been washed. Possible mechanisms for this effect are considered.
The mechanism of bone marrow‐derived (B) lymphocyte activation. II. A “second signal” for antigen‐specific activation provided by flagellin and lipopolysaccharide
Authors: Schrader J. W.
Published: February 2007

Evidence is presented that the activity of polymerized flagellin (POL) in allowing spleen cells from congenitally athymic (nu/nu) mice to respond in vitro to the thymus‐dependent antigen fowl IgG (FGG), is due to an intrinsic property of the POL molecule, rather than to some minor contamination of the preparation by lipopolysaccharide (LPS). While LPS prepared from the same Salmonella strain as was the POL was shown to be active in the present system, the potency of the LPS was not sufficient to account simply for the activity of the POL preparation in the light of its possible endotoxin content. Additionally, the activity of the POL was shown to be susceptible to treatment by the proteolytic enzymes, trypsin and pepsin. Thus, it is shown that two substances, one a protein, the other a LPS, share the property of allowing bone marrow‐derived (B) cells to be triggered by antigen in the absence of thymus‐derived (T) cells. A basis for the common action of LPS and the protein POL was sought in their shared polymeric nature. However, the monomeric form of flagellin, even when oxidized so that it did not repolymerize under stringent conditions, was still active, suggesting that the situation is more complex.
Immunological responses of guinea pigs to a synthetic autoantigen of brain
Authors: Lennon Vanda A. , Carnegie P. R.
Published: February 2007

A synthetic peptide, Ser‐Arg‐Phe‐Ser‐Trp‐Gly‐Ala‐Glu‐Gly‐Gln‐Arg, of identical sequence to residues 112 to 122 of the basic protein of human myelin was active in guinea pigs in inducing experimental autoimmune encephalomyelitis. This peptide did not induce a humoral immune response, but a cellular immune response was obtained, as judged by transformation of splenic lymphocytes when these were cultured with the human encephalitogenic protein, and by demonstration of macrophage inhibitory factor when peritoneal exudate cells were incubated with the protein.
T cell suppression in vitro. I. Role in regulation of antibody responses
Authors: Feldmann Marc
Published: February 2007

Suppression of the antibody response by supraoptimal numbers of T helper cells was studied in vitro and found to have both a specific and a nonspecific component. Suppression did not depend on direct cell contract of T and B cells, as supernatants of activated T cells were just as inhibitory. Suppression by excess T cells (or T cell supernatant) was abrogated by the addition of macrophages. By using a tolerance induction protocol, it was shown that T cell supernatants induce partial tolerance in both T and B cells. This tolerance occurred in three different experimental settings – if adherent cells were physically removed by surface adherence, in the presence of anti‐macrophage serum, or in the presence of very high concentrations of T cell supernatant. All three conditions stress the importance of the interaction between T cell supernatants and macrophages.

The nonspecific form of suppression was not analyzed in detail here, but was also shown to be partly abrogated by macrophages, suggesting that it may be analogous to antigenic competition, one model of which has recently been shown to be abolished by addition of macrophages. The results suggest the presence of homeostatic feedback loops, due to excess T cell function – T cell products suppress the function of T cells, preventing the induction of further helper cells, and also suppress B cells directly. The balance between T cell suppression and cooperation is affected by macrophage function.
An allotypic marker on chicken immunoglobulin M
Authors: Pink J. R. L.
Published: February 2007

An allotypic marker, present on IgM, but not IgG, molecules in sera from chickens of the inbred CA, CB and G‐B1 lines, is described. The marker, called “C‐Ml”, is absent in sera from birds of the WA and WB lines, and its segregation in (CB × WA)F2 birds is consistent with its inheritance as a single dominant factor. It can be detected in sera of normal (CA) one‐week‐old birds. The locus controlling this allotype marker is not sex‐linked, nor is it closely linked to the serum albumin, dominant white feather color, or B blood group and major histocompatibility loci.
The kinectics of proliferation and maturation of mitogen‐activated bone marrow‐derived lymphocytes
Authors: Melchers F. , Andersson J.
Published: February 2007

The B cell mitogens lipopolysaccharide (LPS), purified protein derivative of tuberculin (PPD) and fetal calf serum (FCS) all stimulate spleen cells from nude mice to increased DNA‐synthesis 14 to 16 h after the initiation of mitogenic stimulation. The three mitogens also induce the maturation of B cells to plaque‐forming cells (PFC). All three mitogens stimulate largely identical B cell populations. The extent to which B cells are stimulated to DNA synthesis and to the development of PFC varies from mitogen to mitogen.

PFC arise by clonal growth through proliferation and maturation. A “hot pulse” of radioactive thymidine given between 0 and 20 h of stimulation has no effect on the development of PFC during subsequent mitogenic stimulation. Pulses given between 24 and 36 h after stimulation abolish the development of over 90 % of the PFC. The minimum pulse time required for maximum inhibition of the development of PFC during that time is 6 h. Beyond 36 h of stimulation by either of the three mitogens, PFC emerge rapidly. Between 60 and 72 h less than 10 % of all PFC emerging at 72 h are abolished by a “hot pulse”.

The kinetics of the clonal development of PFC after mitogenic stimulation are compared to that of antigenic stimulation. The comparison suggests that B cells stimulated by antigen in the in vivo primary immune response culture system go through a longer period of proliferation than when they are stimulated by mitogen before maturation to PFC.
Papain‐resistant (f) and papain‐sensitive (g) subclasses of rabbit slgA. Allotypic specificities on different domains of the g subclass of α‐chains (αg)
Authors: Malek T. R. , Hanly W. Carey , Knight Katherine L.
Published: February 2007

Secretory IgA (sIgA) from rabbits homozygous for the f71 and g75 allotypic specificities of the f and g subclasses, respectively, was digested into four fractions: sIgA, Fc2α, Fab2α and Fabα. The subclass and allotypic characteristics of each fraction were determined by quantitative radioprecipitation analyses. The f71 allotypic specificities were found predominantly in the undigested sIgA (with some in the Fabα fragment) and the g75 allotypic specificities were in the Fc2α and Fab2α fractions. Previous data from our laboratory indicated that the f72 and f73 sIgA allotypes of the g subclass are resistant to cleavage and that the g74 sIgA allotype of the g subclass is cleaved by papain. The present and previously reported data support the hypothesis that resistance or sensitivity of rabbit sIgA to papain digestion is a function of the subclass rather than the individual allotypic specificities.

Quantitative radioprecipitation analyses of the Fc2α and Fab2α fragments showed that the “g” allotypic specificities are composed of multiple determinants, some of which reside on the Fd part of the α‐chain and some of which reside on the Fc part of the α‐chain. Anti‐allotype antisera have been prepared which are specific for the allotype determinant(s) present on each of the fragments. Of special interest is the ability to serologically distinguish the CH1 domain on the Fd fragment of a rabbit α‐chain.
Inhibition of lymphocyte proliferative responses by anti‐HL‐A alloantisera
Authors: Brochier J. , Roitt I. M. , Festenstein H.
Published: February 2007

Anti‐HL‐A sera from women immunized by pregnancy, inhibit the proliferative response in mixed lymphocyte cultures. Inhibition is not necessarily related to the presence of lymphocyte HL‐A antigens corresponding to the cytotoxic antibodies demonstrable in these sera. Analysis of the results and appropriate absorption studies are indicative of other noncytotoxic inhibitory antibodies with non‐HL‐A specificity; the presence of antibodies directed against antigens on lymphocytes from male as distinct from female donors, and other as yet unidentified antigens is demonstrated. At low concentrations, these antibodies inactivate the stimulating cells; after suitable absorption of non‐HL‐A antibodies, cytotoxic anti‐HL‐A antibodies are seen to inhibit only stimulating cells carrying the relevant HL‐A antigens. At higher antiserum concentrations the responding cells are also inhibited; it is not clear, however, if anti‐HL‐A antibodies contribute to this effect. PPD‐induced transformation is also inhibited by non‐HL‐A antibodies, HL‐A antibodies being effective (if at all) only at high concentration. Inhibition is not mediated by inactivation of adherent cells. The mechanism of the inhibitions and the possible relationship between the strong MLR locus and the Ir gene product is discussed.
Inhibition of mitogenic stimulation of mouse lymphocytes by anti‐mouse immunoglobulin antibodies. I. Mode of action
Authors: Andersson J. , Bullock W. W. , Melchers F.
Published: February 2007

Antibodies with specificities for mouse μ‐chains and mouse ϰ‐ and λ‐chains inhibit the stimulation of the major fraction of splenic lymphocytes from nude mice by lipopolysaccharide (LPS), by the purified protein derivative of tuberculin (PPD) and by fetal calf serum (FCS) to differentiate into immunoglobulin (Ig)‐secreting, plaque‐forming cells (PFC). Antibodies with specificities for mouse γ‐chains of with Ig‐unrelated specificities (anti‐ovalbumin, anti‐E. coli β‐galactosidase) do not elicit this inhibition. Bivalent pepsin (Fab')2 fragments mediate the same inhibition at the same concentrations, while monovalent papain Fab fragments of such anti‐Ig antibodies have a 100‐fold lower capacity to inhibit differentiation into PFC. Rabbit as well as chicken anti‐Ig antibodies are inhibitory; this indicates that the inhibition is not complement‐mediated. Cells stimulated for 6 h by LPS can no longer be inhibited by anti‐Ig antibodies from differentiating to PFC, a finding which indicates that changes take place in the mitogen‐stimulated cells which may involve surface‐bound Ig molecules. Inhibition can be abrogated, but only prior to the addition of mitogen to the cells, by proteolytic treatment of the cells or by dissociation of the anti‐Ig antibodies in excess medium with time from the cells.

Inhibition of DNA synthesis by anti‐Ig antibodies in splenic lymphocytes is more complex and will be described in a subsequent publication.
IgD and IgM on the membrane of lymphoid cells in macroglobulinemia. Evidence for identity of membrane IgD and IgM antibody activity in a case with anti‐IgG receptors
Authors: Pernis B. , Brouet J. C. , Seligmann M.
Published: February 2007

Monoclonal B lymphocyte populations from the bone marrow of seven cases of Waldenström's macroglobulinemia were studied for membrane IgD and IgM. In all cases lymphocytes with both classes on the membrane were found as well as cells with IgD or IgM only; the relative percentages of these three groups of lymphocytes were different in different cases. The IgM‐containing plasma cells always had membrane IgM and some of these also had IgD. Of particular interest was one patient whose macroglobulin had an anti‐IgG reactivity. The peripheral blood B lymphocytes of this patient had both membrane IgM and membrane IgD: it was possible to show, by capping with anti‐IgG or with aggregated IgG, that both classes of immunoglobulin receptors shared reactivity with human IgG.
Enhancement of the expression of histocompatibility antigens of mouse lymphoid cells by interferon in vitro
Authors: Lindahl Pernilla , Leary Patricia , Gresser I.
Published: February 2007

The expression of surface antigens of thymocytes and splenic lymphocytes was determined by quantitative absorption of alloantibodies. Mouse interferon preparations enhanced the expression of histocompatibility antigens of thymocytes from mice of different ages, but of splenic lymphocytes only from young mice. Interferon did not affect the expression of the theta antigen of thymocytes or splenic lymphocytes.
Nonspecific suppression of T lymphocyte responses in mice carrying progressively growing tumors
Authors: Kilburn D. G. , Smith J. B. , Gorczynski R. M.
Published: February 2007

Unfractionated spleen cells from mice with four different types of progressively growing tumors were unable to show enhanced DNA or protein synthesis upon stimulation with phytohemagglutinin (PHA) in vitro. After separation by velocity sedimentation, or passage over an anti‐immunoglobulin column, cells were obtained which could respond to this mitogen. An auxiliary population of cells obtained by velocity sedimentation, sedimenting with the characteristics of activated B lymphocytes and sensitive to the cytotoxic effects of anti‐immunoglobulin serum and complement, could depress the response of normal spleen cells challenged with PHA. A role for this cell type in the tumor progression seen in the host animals is discussed.
T cell suppression of contact sensitivity in the mouse. III. The role of macrophages and the specific triggering of nonspecific suppression
Authors: Asherson G. L. , Zembala M.
Published: February 2007

Passive transfer of contact sensitivity and suppression of contact sensitivity by lymph node cells is abolished by treatment with anti‐Θ serum and complement. In contrast, both these forms of passive transfer by peritoneal exudate cells resist treatment with anti‐Θ serum but are abolished by trypsin. This suggests that the cell responsible in the peritoneal exudate is a macrophage or other Θ‐negative cell.

Peritoneal exudate cells can be armed for suppression by incubation in suppressor supernatant and a similar cell is probably responsible. Double transfer experiments show that suppressor lymph node cells produce factor(s) in vivo which inhibit “macrophage‐mediated transfers” of skin reactions.

The specificity of the passive transfer of suppression by suppressor lymph node cells, suppressor peritoneal exudate cells, and peritoneal exudate cells armed for suppression was studied. All systems were specific in that the cells failed to suppress passive transfer of contact sensitivity to 4‐ethoxy‐methylene‐2‐phenyloxazolone (Ox) when the recipients were challenged with Ox. However, in the peritoneal exudate cell systems but not in the lymph node system, nonspecific suppression occurred when mice were challenged with a mixture of two antigens – picryl chloride corresponding to the suppressor cells, and Ox corresponding to the cells mediating passive transfer. The hypothesis is put forward that lymphocytes convey a factor to macrophages which enables them, in the presence of antigen, to suppress the passive transfer of contact sensitivity nonspecifically.
Carbon Nanotube Composite as Novel Platform for Microbial Biosensor
Authors: Kirgoz Ülkü A. , Timur Suna , Odaci Dilek , Pérez Briza , Alegret Salvador , Merkoçi Arben
Published: February 2007

The presented work includes the development of a microbial biosensor based on a carbon‐nanotube epoxy composite (CNTEC) platform used as supporting electrode for cell immobilization. For this purpose, cells of Pseudomonas fluorescens were immobilized on the surface of the CNTEC electrode by means of gelatin which was then cross linked with glutaraldehyde. After optimization of experimental parameters like cell amount, pH and temperature, the system was calibrated for glucose. From the calibration graph the linear range was estimated as 0.5–4.0 mM with a response time of 100 s. Furthermore, substrate specificity and operational stability were investigated. Finally, the results that were obtained with CNTEC electrodes were compared with conventional graphite epoxy composite electrode (GECE) and as a result, higher current values (2 to 3 folds) were observed with CNTEC microbial biosensor.
A voice crying in the wilderness: Legislative oversight agencies' efforts to achieve utilization
Authors: VanLandingham Gary R.
Published: February 2007

Although evaluation utilization literature has identified a wide range of practical actions that evaluators can take to maximize use of their work by policymakers, an emphasis on organizational independence can limit use of these strategies. This can restrict evaluators' role to that of a voice crying in the wilderness rather than speaking truth to power.
Using a crystal ball instead of a rear‐view mirror: Helping state legislators assess the future impacts of major federal legislation
Authors: Alter Joel , Patterson John
Published: February 2007

This chapter discusses the possible use of prospective evaluation by a legislative oversight agency. It illustrates reasons and methods for estimating future impacts of the No Child Left Behind Act.
The impact of state physical education requirements on youth physical activity and overweight
Authors: Cawley John , Meyerhoefer Chad , Newhouse David
Published: February 2007

To combat childhood overweight in the US, which has risen dramatically in the past three decades, many medical and public health organizations have called for students to spend more time in physical education (PE) classes. This paper is the first to examine the impact of state PE requirements on student PE exercise time. It also exploits variation in state laws as quasi‐natural experiments in order to estimate the causal impact of PE on overall student physical activity and weight. We study nationwide data from the Youth Risk Behavior Surveillance System for 1999, 2001, and 2003 merged with data on state minimum PE requirements from the 2001 Shape of the Nation Report.

We find that high school students with a binding PE requirement report an average of 31 additional minutes per week spent physically active in PE class. Our results also indicate that additional PE time raises the number of days per week that girls report having exercised vigorously or having engaged in strength‐building activity. We find no evidence that PE lowers BMI or the probability that a student is overweight.

We conclude that raising PE credit requirements may make girls more physically active overall but there is not yet the scientific base to declare raising PE requirements an anti‐obesity initiative for either boys or girls. Copyright © 2007 John Wiley & Sons, Ltd.
The role of ‘reference goods’ in contingent valuation: should we help respondents to ‘construct’ their willingness to pay?
Authors: Smith Richard D.
Published: February 2007

A general population sample of 135 Australian respondents completed one of four contingent valuation surveys that asked them to value health benefits either in the absence of an explicit reference good or in the presence of one of three different forms of reference good. Results suggest that respondents have a ‘ball‐park’ figure that is then challenged by the reference good. For values that appear far lower than, or similar to, this ‘ball‐park’ figure, the reference good has littlequantitativeeffect, butqualitativelyappears to help respondents in their confidence in this value being their actual WTP. The implications for CV research in health care are outlined in the discussion. Copyright © 2007 John Wiley & Sons, Ltd.