bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison with monoclonal anti‐Ia antibodies of antigenic determinants inducing lymphocyte proliferation and immune interferon production in primary and secondary murine mixed lymphocyte reactions
Authors: Landolfo Santo , Kirchner Holger
Published: February 2007

The nature of Ia antigens inducing lymphocyte proliferation and immune interferon (IFN‐γ) production in primary and secondary murine mixed lymphocyte cultures was studied by means of monoclonal anti‐Ia antibodies. In primary mixed lymphocyte cultures, both lymphocyte proliferation and IFN‐γ production were found to be controlled by Ia determinants coded for by the I‐A subregion. E alloantigen‐recognizing antibodies displayed consistent stimulation of both lymphocyte functions, instead of inhibition, suggesting a regulatory mechanism of the E molecule on lymphocyte activation. In secondary mixed lymphocyte cultures fewer Ia determinants seemed to be involved in lymphocyte proliferation, since only antibodies directed against specificities Ia.17 and Ia.19 were found capable of blocking lymphocyte proliferation. In contrast, IFN‐γ production, although significantly decreased by antibodies against specificities Ia.17 and Ia.19, was not completely abrogated, even by a mixture of all anti‐Ia antibodies.

The data indicate that (a) in primary mixed lymphocyte reaction lymphocyte proliferation and IFN‐γ production are triggered by the same Ia specificities coded by the I‐A subregion and (b) in secondary mixed lymphocyte reaction, whereas lymphocyte proliferation is restricted to fewer determinants, IFN‐γ production shows a lower threshold of activation, being induced also by determinants ‘silent’ in primary mixed lymphocyte reaction.
An example of major histocompatibility complex‐linked control of idiotypic interactions
Authors: Holmberg Dan , Ivars Fredrik , Coutinho Antonio
Published: February 2007

Normal euthymic mice, injected i.v. with low doses of syngeneic monoclonal antibodies carrying “recurrent” idiotypes, develop a specific increase in numbers of splenic IgM plaque‐forming cells that are paratopically and idiotypically similar to the injected antibody. We have now studied the responsiveness to a C57BL/6 anti‐dextran α(1 → 6) and BALB/c anti‐TNP (trinitrophenyl) monoclonal antibodies in a variety of strains. It was found that such responses are controlled by two linkage groups, namely major histocompatibility complex (MHC) and Ig‐1.
Immunosuppression caused by antigen feeding II. Suppressor T cells mask Peyer's patch B cell priming to orally administered antigen
Authors: Macdonald Thomas Thornton
Published: February 2007

Peyer's patch (PP) cells transferred into sublethally irradiated recipients generated substantial IgM, IgG and IgA anti‐sheep red blood cell (SRBC) plaque‐forming cell (PFC) responses in the recipient spleen. If donor mice were given SRBC orally for 4–5 weeks prior to transfer, the adoptively transferred PP IgG and IgA responses were considerably suppressed, although the IgM responses were often unaffected. Co‐injection of PP cells from antigen‐fed mice with PP cells from normal mice resulted in marked suppression of the normal PP IgG and IgA response. However, treatment of PP cells from antigen‐fed mice with anti‐Thy‐1.2 plus complement prior to cotransfer completely abrogated suppression of the IgG PFC response and partially abrogated the suppressed IgA response. B cells from the PP of antigen‐fed mice, when transferred into SRBC‐primed irradiated recipients (to provide T cell help) generated 2–3 times more IgG and IgA PFC than comparable numbers of B cells from the PP of normal mice. Thus antigen feeding generates suppressor T cells in PP which can mask the expression of B cell priming to orally administered antigen.
Thymic reticulum in mice II. Culture and characterization of nonepithelial phagocytic cells of the thymic reticulum: Their role in the syngeneic stimulation of thymic medullary lymphocytes
Authors: Papiernik Martine , Nabarra Bernadette , Savino Wilson , Pontoux Christiane , Barbey Sylvette
Published: February 2007

In the present report the characteristics of nonepithelial phagocytic cells of the murine thymic reticulum are described. Primary cultures were established from thymic fragments. Nonadherent cel s with hairy membranes proliferated on the surface of established primary monolayers. These cells were recovered and replated in secondary cultures were they appeared as large adherent cells with dendritic shape. At the electron microscopic level, phagocytic cells of the thymic reticulum in culture (P‐TR‐C) appear as clear vacuolated cells with an indented nucleus and few lysosomes; this morphological aspect makes them different from the common macrophage, despite their phagocytic capacity. P‐TR‐C are positive for nonspecific esterase, acid phosphatase which is found in the few lysosomes present, 5′‐nucleotidase and α‐D‐mannosidase, but negative for peroxidase. A high proportion of α‐mannosidase‐positive cells is inconsistent with the common macrophage, but in common with other cells with dendritic shape such as Langerhans cells. They are Thy‐1−, Ig− and nearly half of them are IA+. P‐TR‐C can be defined as the stimulator cells for syngeneic stimulation; they are able to induce the proliferation of lymphocytes enriched in mature syngeneic medullary thymocytes, but not in immature cortical ones. Characteristics of P‐TR‐C make them very similar to the interdigitating cells described in the peripheral lymphoid organs and in the thymus in situ.
Differential expression of HLA‐DR and DR‐linked determinants on human leukemias and lymphoid cells
Authors: Newman Roland A. , Delia Domenico , Greaves Melvyn F. , Navarrete Christina , Fainboim Leonardo , Festenstein Hilliard
Published: February 2007

Leukemic and normal hemopoietic cells were examined with the monoclonal antibodies DA2 and Genox 353 for the presence of HLA‐DR and DR‐linked (DC/MB) determinants, respectively. Although most non‐T acute leukemias and leukemic cell lines expressed the monomorphic DR determinant detected by DA2, fewer than expected expressed the DR‐linked polymorphic specificity detected by Genox 353. TdT+ lymphoid precursors from normal bone marrow were also DA2+ but Genox 353−. T cells and thymocytes which were DA2−, Genox 353− became DA2+, Genox 353+ after activation in vitro.

Immunoprecipitation using DA2 and Genox 353 gave bands on polyacrylamide gelelectrophoresis which were of different molecular weights. In addition, DA2 could absorb out Genox 353 determinants from a cell lysate whereas Genox 353 could not absorb out DA2 determinants. It is concluded that DA2 and Genox 353 detect HLA‐DR and DR‐linked (DC1/MB1) determinants, respectively, and that these are differentially expressed on hemopoietic cells during differentiation.
Flow microfluorometric analysis of mouse thymus development in vivo and in vitro
Authors: Ceredig Rhodri , MacDonald H. Robson , Jenkinson Eric J.
Published: February 2007

The phenotypic properties of lymphoid cells in the developing embryonic thymus were characterized using monoclonal antibodies and flow microfluorometry. CBA/J‐T6/T6 thymocytes stained with antibodies directed against Thy‐1.2, Lyt‐1, Lyt‐2 or H‐2Kk were simultaneously analyzed for fluorescence intensity and forward light scatter (FLS), a cell size‐related parameter. Whereas Thy‐1 and Lyt‐1 antigens were already present on 15‐day fetal thymocytes, Lyt‐2 expression was first detectable on day 16 and increased rapidly thereafter to reach adult levels by day 19. Concomitant with these phenotypic changes, rapid changes in FLS occurred during this time period. The FLS distribution of Lyt‐2+ cells was initially homogeneously high (day 16) but became biphasic at days 17–18. Thereafter, the lower FLS subpopulation predominated. FLS changes in Lyt‐2− cells could be dissociated kinetically from changes in the Lyt‐2+ subpopulation. Thus high FLS Lyt‐2− cells were the predominant subpopulation throughout the entire fetal period and could still be detected after birth, when a population with lower FLS first appeared. The embryonic thymus developing in vivo was then compared with the 13‐day embryonic thymus maintained for 14 days in an in vitro organ culture system. Based on a combination of fluorescence and FLS analysis, the organ‐cultured thymus appeared to share certain phenotypic properties with the 18–19 day in vivo developing thymus.
B lymphocyte activation: Entry into cell cycle is accompanied by decreased expression of IgD but not IgM
Authors: Monroe John G. , Havran Wendy L. , Cambier John C.
Published: February 2007

To gain insight into the function of cell surface IgM (sIgM) and IgD (sIgD), the expression of these markers on B lymphocytes was quantitated during activation and progression through the cell cycle. Specifically, analysis and correlation of changes in cell cycle state, sIgM and sIgD expression and cell size following exposure of murine B cells to mitogenic levels of lipopolysaccharide and dextran sulfate is reported. As assessed by flow cytometric acridine orange analysis, a large proportion of normal splenic B cells respond within 48 h of exposure to these mitogens by entry into the cell cycle. This response is accompanied by an increase in cell size as determined by flow cytometric “time of flight” measurement. Flow cytometric immunofluorescence analysis reveals a simultaneous alteration in sIg expression. Specifically, cells leaving G0 and transiting G1 increase in diameter from 5 μm to 6 μm and lose > 80% of sIgD while sIgM remains constant. Progression through the remainder of the cell cycle is accompanied by a further increase in mean cell diameter to approximately 12 μm while sIgM and sIgD levels remain at G1 levels. The abrupt loss of sIgD as cells transit G1 suggests that an active process mediates this decrease.
Interferon‐γ production by Listeria monocytogenes‐specific T cells active in cellular antibacterial immunity
Authors: Kaufmann Stefan H. E. , Hahn Helmut , Berger Rudolf , Kirchner Holger
Published: February 2007

Cultures of peritoneal exudate T lymphocyte‐enriched cells (PETLEC) from Listeria monocytogenes‐immune mice, antigen‐presenting cells (APC) and heat‐killed L. monocytogenes produced high amounts of interferon‐γ (IFN‐γ). High IFN titers were also observed after stimulation of L. monocytogenes‐immune cell cultures with the T cell mitogens concanavalin A and phytohemagglutinin. L. monocytogenes‐immune PETLEC produced several fold higher IFN titers than normal cell cultures in response to mitogen and antigen. Under both circumstances, APC were required for optimum responses. L. monocytogenes‐immune PETLEC participating in IFN production were Lyt 1+23−. IFN‐γ was also produced in cultures of cloned L. monocytogenes‐specific T cells. Since the same T cell clone showed antigen‐specific proliferative responses and interleukin production in vitro, and could adoptively mediate delayed‐type hypersensitivity and anti‐listerial protection in vivo, it is suggested that IFN production is a function of specific T cells active in cellular antibacterial immunity.
Marker of peripheral blood granulocytes and monocytes of man recognized by two monoclonal antibodies VEP8 and VEP9 involves the trisaccharide 3‐fucosyl‐N‐acetyllactosamine
Authors: Gooi Hock C. , Thorpe Susan J. , Hounsell Elizabeth F. , Rumpold Helmut , Kraft Dietrich , Förster Othmar , Feizi Ten
Published: February 2007

Two hybridoma antibodies (VEP8 and VEP9) raised against the promyelomonocytic leukemia cell line HL60 have previously been shown to distinguish human granulocytes and monocytes from other cells of the peripheral blood. We report here that both antibodies recognize the carbohydrate structure 3‐fucosyl‐N‐acetyllactosamine with the following sequence: magnified image This structure is the same as that recognized by a hybridoma antibody against mouse teratocarcinoma cells (anti‐SSEA‐1) which recognizes an early embryonic antigen in the mouse. Until recently this carbohydrate structure was considered to be rare among glycoproteins and glycosphingolipids. However, there is a growing list of human and animal glycoproteins in which this sequence has been detected by chemical and immunochemical methods. In this article we survey this information and discuss how this and other carbohydrate structures behave as differentiation‐ or tumor‐associated antigens.
The expression of a set of antibody variable regions in lipopolysaccharide‐reactive B cells at various stages of ontogeny and its control by anti‐idiotypic antibody
Authors: Nishikawa Shin‐Ichi , Takemori Toshitada , Rajewsky Klaus
Published: February 2007

An analysis is presented in which we measure the expression of a subset of antibody variable (V) regions in lipopolysaccharide (LPS)‐reactive precursor B cells at various stages of ontogeny. The V regions were characterized by hapten (4‐hydroxy‐3‐nitrophenyl)acetyl (NP)‐binding specifity and/or expression of idiotypic determinants whose genetic basis had been explored in previous studies. Only V regions containing the Vλ1 domain were considered: this allowed an unequivocal determination of idiotopes and reduced heterogeneity in the system essentially to the multiplicity of VH and D genes.

It was found that approximately every fourth λ1‐bearing LPS‐reactive splenic B cell produces an NP‐binding antibody. Approximately 1 in 40 λ1‐bearing cells expressed an idiotope (Ac38) which is encoded by Vλ1 and a set of related VH genes in combination with D and J elements. Of these cells, only a minority produce an NP‐binding antibody and a few percent of the latter express a second idiotope (Ac146) which is known to be restricted to a subset of Ac38‐positive, NP‐binding humoral antibodies. All these frequencies are in good accord with previous analyses of anti‐idiotopeinduced antibodies in the serum. They can be easily accommodated into a simple model of random selection of VH genes in LPS‐reactive B lymphocytes.

The frequencies of the V regions under study were essentially the same in LPS‐reactive B cells from spleens of adult and newborn animals and in LPS‐reactive B cells generated from bone marrow pre‐B cells in vitro. In the case of the latter cells the frequencies were independent of the absence or presence of T cells in the culture system.

While we could thus detect, in naive mice, neither positive nor negative selection of the cells from the time of their generation in the bone marrow until their arrival in the periphery, negative selection is in principle possible: the presence of microgram amounts of anti‐idiotope antibodies during maturation from pre‐B to B cells specifically blocks the appearance of idiotope‐bearing LPS‐reactive cells in vitro. The potential physiological role of the latter effect in the sense of self‐stabilization of the expressed antibody repertoire in ongoing immune responses and the possibility that frequency determinations in LPS‐reactive B cells may be not representative for the repertoire expressed in the population of mature B cells is discussed.
T lymphocyte lines producing or vaccinating against autoimmune encephalomyelitis (EAE). Functional activation induces peanut agglutinin receptors and accumulation in the brain and thymus of line cells
Authors: Naparstek Yaakov , Ben‐Nun Avraham , Holoshitz Joseph , Reshef Tamara , Frenkel Ayala , Rosenberg Mireille , Cohen Irun R.
Published: February 2007

We studied lines of rat T cells, specifically reactive against myelin basic protein (BP), that were functional in mediating autoimmune encephalomyelitis or in vaccinating rats against induction of active EAE. Herein we report that these functions depended on activation of the cells by incubation with BP or with a T cell mitogen prior to inoculation into recipient rats. Activation was accompanied by the exposure of membrane‐binding sites specific for the lectin peanut agglutinin. Accumulation of activated line cells in the central nervous system and thymus gland was observed.
Spontaneous increase of DNA turnover in murine systemic lupus erythematosus
Authors: Golan Dov T. , Borel Yves
Published: February 2007

DNA synthesis and release was studied in unstimulated splenocytes of strains of mice known to develop spontaneous systemic lupus erythematosus (SLE)‐like disease and in non‐SLE age‐ and sex‐matched strains as well. Newly synthesized DNA was measured as total acid‐insoluble radioactive material present in cell pellet plus supernatant of unstimulated 0–72 h cell cultures [3H]thymidine‐pulsed, whereas DNA release was measured as amount of acid‐precipitable radioactivity found in supernatant of those cultures. In all strains known to develop spontaneous murine SLE the amount of newly synthesized DNA was 1.3–2.1‐fold increased when compared to normal strains studied concomitantly. Furthermore, a significant increase in DNA release into medium, unrelated to cell viability, was observed in those strains as well. These observations clearly demonstrate different metabolic rates of synthesis and release of DNA in murine SLE. This difference suggests the existance of an underlying mechanism responsible for extracellular DNA abundancy, which may be important for the formation of circulating DNA‐anti‐DNA immune complexes.
Interferons as macrophage‐activating factors. II. Enhanced secretion of interleukin 1 by lipopolysaccharide‐stimulated human monocytes
Authors: Arenzana‐Seisdedos Fernando , Virelizier Jean‐Louis
Published: February 2007

Human adherent monocytes were incubated with interferon (IFN) preparations, then washed and stimulated with endotoxins. The interleukin (IL1) activity in the supernatants of IFN‐treated monocyte cultures was found to be increased as compared to control (not pretreated) cultures. This phenomenon was observed whether α or β IFN was used, and was completely abolished by antiserum to the relevant IFN. IL1 secretion of IFN‐treated monocyte cultures could be triggered by suboptimal dosis of endotoxins, unable to induce any IL1 activity in control medium‐treated cultures. IFN was highly efficient in this system, since very low concentrations (of the order of 2 units) were effective. Since IFN alone, without endotoxin stimulation, was unable to induce IL1 secretion, the results indicate that IFN is able to activate monocytes, by inducing a potential secretory capacity rather than an ongoing IL1 secretion function. The ability of IFN to enhance the IL1 secretory potential of human monocytes may be relevant to the known immunoenhancing effects of IFN preparations and to the pyrogenic effects of IFN administration in patients.
Agglutination of murine and guinea pig peritoneal cells by α‐L‐fucose‐binding lectin: Evonymus europaea
Authors: Petryniak Jerzy , Duśa Danuta , Podwińska Jadwiga
Published: February 2007

Among lectins from Lotus tetragonolobus, Ulex europaeus I and Evonymus europaea, agglutinating cells with blood group H determinants containing L‐fucose α1→2‐linked to subterminal D‐galactose, only the last lectin agglutinates thioglycolate‐ and paraffin oil‐stimulated murine and guinea pig peritoneal exudate cells (PEC). The agglutination is inhibited by specific inhibitors of Evonymus lectin only: lacto‐N‐fucopentaose I and lactose. These results suggest the presence of a determinant on the surface of PEC, containing L‐fucose α1‐linked at the nonreducing end which is different from blood group H determinants. Nonstimulated murine peritoneal cells (PC) are not agglutinated by the lectin but become agglutinable after neuraminidase treatment. Unstimulated guinea pig PC from different animals are agglutinated to a different extent by the same lectin concentration and show increased agglutinability after neuraminidase digestion. These results show that receptor for Evonymus lectin also exists on the nonstimulated PC but access to it is hindered by sialic acid. Trypsin‐ and pronase‐digested PEC show increased agglutinability with Evonymus lectin. These results suggest that the lectin receptor is a glycolipid.

Since α‐linked L‐fucose has been suggested as a part of the macrophage receptor for migration inhibitory factor in the guinea pig (Remold, J. Exp. Med. 1973. 138: 1065), the effect of Evonymus europaea lectin on the migration of PEC was studied. It was found that lectin inhibits the migration of PEC in the capillary tube assay up to 80%.
Role of human factor I and C3b receptor in the cleavage of surface‐bound C3bi molecules
Authors: Medicus Rudolf G. , Melamed Julian , Arnaout M. Amin
Published: February 2007

Control of functions mediated by the third component of complement (C3) depends on the rate of generation and degradation of biologically active C3 fragments. To evaluate the mechanisms of degradation of active C3 fragments, the role of the control protein C3b/C4b inactivator (factor I) was investigated under conditions approximating those found in vivo, i.e. in the presence of plasma. The breakdown of human erythrocyte‐bound C3bi molecules in serum or plasma was mediated only by factor I, since factor I‐deficient or ‐depleted plasma was inactive until reconstituted with highly purified factor I. The rate of cleavage of C3bi bound to human erythrocytes by purified factor I was not affected by the presence or absence of β1H (factor H). The released breakdown product of C3bi has been shown to be C3c antigenically and on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Two different monospecific antibodies to the human C3b receptor totally abrogated factor I‐mediated cleavage of cell‐bound C3bi, suggesting that the C3b receptor (but not factor H) is required as an obligate cofactor. The rate of this C3b receptor‐dependent, factor I‐mediated cleavage of bound C3bi is strongly regulated by the surface to which C3bi is bound. Whereas C3bi bound to particulate nonactivators of the alternative complement pathway such as human erythrocytes is rapidly degraded by this mechanism, the rate of cleavage of C3bi bound to activators is significantly slower. These data suggest a physiologic role of C3b receptors in the degradation of biologically active C3 fragments deposited on host tissues. They also suggest that C3bi molecules on restricted surfaces are relatively stable and can thereby interact with complement C3 receptors in vivo.
Properties of human natural interferon‐producing cells stimulated by tumor cell lines
Authors: Rönnblomo Lars , Ramstedt Urban , Alm Gunnar V.
Published: February 2007

Human peripheral blood mononuclear leukocytes cocultured with WISH human amnion cells or K562 tumor cells rapidly produce interferon‐α (IFN). In the present report we characterize the IFN‐producing cells (IPC) in this system by cell separation procedures, including panning with different monoclonal antibodies. Two types of cells which were responsible for the IFN production could be identified. The first IPC was classified as monocyte/macrophage because it was present in plastic‐adherent cells and apparently carried the OKM1 antigenic marker. T and B lymphocytes were not involved in the IFN production. The second type of IPC was nylon wool‐nonadherent, sheep erythrocyte rosette‐negative, at least partly Fc receptor‐negative and resided in light Percoll density gradient fractions. The natural killer activity and IFN‐producing capacity was studied in such cells fractionated by the panning technique, utilizing HNK‐1, OKT10 and OKM1 antibodies. When WISH and K562 were used as IFN inducers, HNK‐1+ and OKT10+ cells with lytic activity against K562 produced little or no IFN. The IPC were instead confined to HNK‐1− and OKT10− cells. With cells fractionated with respect to the OKM1 antigen, natural killer activity against K562 and WISH cells and IFN production stimulated by K562 cells resided in the OKM1+ cells. In marked contrast, cells producing IFN in response to WISH cells were OKM1−.

The results therefore demonstrate a dissociation between natural killer cells against tumor cells and IPC stimulated by the same targets, suggesting that for at least certain targets/inducers they may represent distinct entities.
Requirement for macrophages or for macrophage‐ or T cell‐derived factors in the mitogenic stimulation of murine B lymphocytes by lipopolysaccharides
Authors: Corbel Catherine , Melchers Fritz
Published: February 2007

Splenic B cells from a variety of mouse strains could be depleted of accessory cells by removal of large cells through velocity sedimentation, followed by adherence to plastic and by passage over Sephadex G‐10. Such accessory cell removal abolished the reactivity of the splenic B cells to the mitogen lipopolysaccharide (LPS), as measured by their capacity to polyclonally proliferate and mature to IgM‐secreting cells. Accessory cells from different sources, such as peritoneal exudate cells, irradiated spleen cells, cells of the macrophage line P388 D1 and macrophages from a single colony grown from bone marrow precursors in semi‐solid media in the presence of colony‐stimulating factor all reconstituted LPS reactivity of the accessory cell‐depleted B cells. Limiting dilutions of the cells of a single macrophage colony indicated that as little as 30 to 1000 macrophages can reconstitute the polyclonal response of 3 × 104 B cells to LPS. Not only activated macrophages, but also activated long‐term helper T cell lines and T cell hybridomas, produced supernatant factors which could also restore responsiveness of depleted B cells to LPS.
The cellular compartmentalization of macrophage‐associated nominal antigen: immunologically relevant macrophage‐associated antigen may not require an intracellular phase of macrophage handling
Authors: Malek Thomas R. , Clement Loran T. , Shevach Ethan M.
Published: February 2007

It has been hypothesized that internalization and “processing” of the nominal antigen by antigen‐presenting cells may be a mandatory event in antigen handling prior to cell surface presentation of the immunologically relevant moiety to T lymphocytes. In previous functional and immunochemical analyses of macrophage (MΦ)‐associated nominal antigen, we obtained data strongly suggesting that an immunologically relevant pool of antigen was detectable on the surface of MΦ pulsed with a soluble protein antigen and then aged for 3–24 h. To provide further information about requisite events of MΦ antigen handling, we have attempted in this study to determine the origin of the nominal antigen associated with the surface of the pulsed‐aged cell using the terpolymer L‐glutamic acid, L‐lysine, L‐tyrosine (GLT) as the antigen. The surface‐bound GLT, after a 24‐h culture, appeared to be derived from GLT initially surface‐associated after the pulse. No evidence was obtained to support the notion that a significant quantity of GLT, initially internalized after the pulse exposure, was recompartmentalized to the cell surface. The turnover of cell‐surface GLT resembled the turnover of MΦ membrane proteins in general. These results, therefore, imply that the crucial events of MΦ antigen handling of GLT may entirely be a cell surface phenomenon.
Mitogenic effect of anti‐Friend leukemia virus antiserum on T cells
Authors: Senn Hans‐Peter , Papoian Ruben
Published: February 2007

It has been previously reported that goat‐ and rat antisera directed against Friend leukemia virus (aFLV) are mitogenic for some B cells, but not for T cells. Here we report that activation of T cells by concanavalin A (Con A) rendered T cells responsive to the mitogenic activity of aFLV. This activity was contained in the immunoglobulin fraction and could be absorbed by purified FLV preparations. Optimal conditions for measuring the mitogenc activity of aFLV include 48 h preincubation of thymocytes with 3 μg/ml Con A followed by reculturing the activated thymocytes for 28 h with aFLV. The acquisition of an aFLV‐responsive state was dependent on early protein synthesis during the Con A‐induced activation period. aFLV did not substitute for interleukin 2 (IL2) in a costimulator assay. Evidence is presented that aFLV acted in a cocultivation assay via growth factor(s). In contrast to control cultures, aFLV‐treated lymphoblasts contained, in their supernatants, IL2 activity as demonstrated by their effect on an IL2‐dependent T cell line. The data suggest that aFLV acted upon activated T cells by enhancing the endogenous production and/or release of IL2.
Lack of a requirement for idiotype matching: T cells from mice which cannot produce idiotype support idiotype‐positive antibody response
Authors: Etlinger Howard M. , Heusser Christoph H.
Published: February 2007

A requirement for idiotype matching was reported such that carrier‐primed T helper cells from mice, which are unable to produce an idiotype (idiotype‐negative) because of genetic reasons or adult anti‐idiotype or neonatal anti‐μ antibody treatment, did not provide helper function for an idiotype‐positive antibody response.

We have analyzed the requirement for idiotype matching in the response to phosphorylcholine by using mice which are idiotype‐negative because they were injected with anti‐idiotype antibody shortly after birth. Carrier‐primed T cells from such animals supported idiotype‐positive responses when mixed with normal or primed B cell populations and challenged with appropriate antigen; these responses were quantitatively and qualitatively similar to those obtained with T cells from idiotype‐positive animals. These results demonstrate no requirement for idiotype matching and suggest that the procedure used to establish an idiotype‐negative T cell donor may be decisive in showing a requirement for idiotype matching.
Rheumatoid factors and secondary immune responses in the mouse I. Frequent occurrence of hybridomas secreting IgM anti‐IgG1autoantibodies after immunization with protein antigens
Authors: Van Snick Jacques , Coulie Pierre
Published: February 2007

The involvement of rheumatoid factor (RF)‐secreting cells in normal immune responses was examined by screening hybridomas derived from 129/Sv mice during primary and secondary immune responses against foreign proteins. No RF‐secreting cells were detected during primary responses, but up to 10% of the total number of clones obtained during secondary responses produced IgM with anti‐IgG activity. Like typical mouse RF, these anti‐IgG autoantibodies had a strict isotypic specificity, mostly for IgG1, and a much stronger avidity for immune complexes than for native IgG. The selective activation of IgG1‐specific RF during these secondary immune reactions was not due to fortuitous antigenic similarities between mouse IgG1and the antigens used for immunization, nor did it result from the use of adjuvants for priming, or from contamination of antigen preparations with lipopolysaccharide. It is therefore concluded that, in the 129/Sv mouse, RF production during secondary immune responses is a physiological phenomenon.
Rheumatoid factors and secondary immune responses in the mouse II. Incidence, kinetics and induction mechanisms
Authors: Coulie Pierre , Van Snick Jacques
Published: February 2007

Production of IgM rheumatoid factor (RF) during secondary immune responses was studied in normal mouse strains by measuring RF synthesis in spleen cell cultures. A considerable, although transient, RF response was observed in BALB/c and C57BL/6 mice immunized and i. v. boosted with various protein antigens and with sheep erythrocytes. With most antigens, RF production equalled or exceeded that of antigen‐specific IgM, but it peaked and subsided earlier. No RF production was detected when either priming or boosting was omitted. The isotypic specificity of RF depended upon the antigens used for immunization: all proteins tested stimulated the synthesis of RF specific for IgG1, whereas sheep erythrocytes induced both IgG1‐ and IgG2a‐specific RF. Reconstitution experiments of irradiated naïve C57BL/6 mice with various combinations of syngeneic antibody against human transferrin and primed or unprimed spleen cells indicated that important RF responses could be induced only when antigen was injected into mice that had received both antibody and immune spleen cells.
The occurrence of defined idiotypes on autoantibodies to mouse thyroglobulin
Authors: Male David , Pryce Gareth , Quartey‐Papafio Ruby , Roitt Ivan
Published: February 2007

Anti‐idiotypic antibodies were raised in rabbits to three monoclonal mouse autoantithyroglobulins. Of the idiotypes recognized, one was unique to that monoclonal, while the other two showed evidence of sharing idiotopes with other monoclonal anti‐thyroglobulin (TG) idiotypes, the IgM idiotype in particular being found on nearly half of the hybridomas studied. Two of the idiotypes could be detected in the sera of mice with experimental allergic thyroiditis (EAT), but they constituted only a very small percentage of the total anti‐TG present. In spite of its low levels in EAT mice the D8 idiotype could be induced by injection of anti‐idiotype and TG and in this case it constituted up to 20% of the anti‐TG activity in individual mice, showing a strain‐related association between the idiotype and autoanti‐TG.
Syngeneic sensitization of mouse lymphocytes on monolayers of thyroid epithelial cells V. The primary syngeneic sensitization is under I‐A subregion control
Authors: Salamero Jean , Charreire Jeannine
Published: February 2007

The genetic control of in vitro primary syngeneic sensitization on monolayers of thyroid epithelial cells was investigated both at the level of the responder lymphocytes and that of stimulator thyroid epithelial cells using congenic resistant strains of mice. It clearly appears that similar to the in vivo model of experimental autoimmune thyroiditis induced by thyroglobulin and complete Freund's adjuvant, the optimal stimulation is found when compatibility between thyroid epithelial cells and responder lymphocytes occurs at the I‐A subregion.
Demonstration of a concanavalin A‐induced lymphokine enhancing arginase activity. Effect of presensitization by a skin allograft
Authors: Schneider Elke , Dy Michel
Published: February 2007

In response to concanavalin A (Con A) mouse spleen cells produce increased amounts of urea. This increase results from arginase activity degrading arginine into urea and ornithine. It is mediated by a soluble protein factor, characterized by its heat stability (10 min at 80°C) and a molecular weight of approximately 32000. The factor is produced by T cells and acts on a cell population mainly present in bone marrow and spleen. Splenocytes collected from skin allograft recipients during rejection produce more urea in response to Con A than those obtained from normal or syngeneically grafted mice. The maximum urea increase is observed just before and maintained during rejection, declining rapidly thereafter. This phenomenon is explained (a) by a 10–15‐fold increase in arginase‐enhancing factor production by Con A‐stimulated allograft recipient spleen cells and (b) by an increased responsiveness of these splenocytes to the lymphokine.
Serological evidences for a membrane structure related to human β2‐microglobulin expressed by certain earthworm leukocytes
Authors: Roch Philippe , Cooper Edwin L. , Eskinazi Daniel P.
Published: February 2007

Indirect immunofluorescence performed with 2 polyclonal and 4 monoclonal antibodies directed against human β2‐microglobulin (β2m) revealed the presence of a β2m‐like determinant on the membrane of a subpopulation of earthworm leukocytes classified as weakly adherent acidophils. Two out of the 4 monoclonal antibodies were found to bind to 15% of the earthworm leukocytes. Similar results were obtained with antibodies specific for β2m and isolated by affinity chromatography from either polyclonal antiserum or anti‐β2m hybridoma supernatant. Additional binding inhibition and competition experiments strengthened the results and suggested that the homology between the structure present on earthworm leukocytes and human β2m may be restricted to only one major determinant. The existence of a β2m‐like molecule in earthworms may provide important clues for understanding protein evolution and basic immune mechanisms.
The introduction of one or two 3β‐cholestanyl residues into benzylpenicilloyl‐eicosa‐L‐lysines greatly potentiates their tolerogenicity for anti‐benzylpenicillol IgE antibody formation
Authors: Lüscher Immanuel F. , Weber Ernst , de Weck Alain L.
Published: February 2007

BALB/c mice were repeatedly immunized with microgram doses of benzylpenicilloylated Ascaris protein(s) (BPO9Asc) in alum. At different stages of the immune response, BPO21 eicosa‐L‐lysine or two analogs containing one or two hydrophobic p‐oxymethylbenzyl‐3β‐cholestanyl succinate (OSuco) groups were injected. When injected early in the immune response, the anti‐BPO IgE antibody formation was much more strongly and permanently suppressed by the lipophilic conjugates than by the hydrophilic BPO21 eicosa‐L‐lysine. A similar, but less marked, suppressive effect was observed on the anti‐BPO IgG1 response.

By adoptive cell transfer experiments, it was found that the OSuco‐containing derivatives induce and act via suppressor T lymphocytes, since this cell‐mediated suppression was sensitive to cyclophosphamide or to treatment with anti‐Lyt‐2.2 antibody plus complement.

When these compounds were injected into repeatedly immunized mice producing late ongoing antibody responses no differences in suppression between hydrophilic and hydrophobic derivatives were observed. In this case, the IgE response was suppressed by about 50%, while the IgG1 response was not affected.

These results are compatible with the suggestion that early IgE responses are most sensitive to T cell‐mediated suppression and that T suppressor cells are better induced by lipophilic than by hydrophilic antigens. The late ongoing IgE response, on the other hand, is less amenable to T cell‐induced suppression and tolerogenic effects brought about by plurivalent BPO antigens operate directly on hapten‐specific IgE‐bearing B cells, regardless of their lipophilic character.
Influenza A hemagglutinin‐specific T cell clones strictly restricted by HLA‐DR1 or HLA‐DR7 molecules
Authors: Sterkers Ghislaine , Henin Yvette , Lepage Virginia , Fradelizzi Didier , Hannoun Claude , Levy Jean Paul
Published: February 2007

The antigenic specificities, major histocompatibility complex restrictions and functional properties of influenza virus‐specific proliferative cloned cell lines have been studied. These lines were specific for the H3 hemagglutinin subtype of influenza A viruses. By using a large panel of HLA‐phenotyped antigen‐presenting cells, it was found that the polymorphic structures, defined as DR1 and DR7 molecules, or closely associated structures, function as the restricting elements. We excluded for these lines a possible restricting role of supertypic specificities, known cross‐reacting elements on DR molecules, or products of other loci in known linkage disequilibrium with the HLA‐DR molecules. Such exquisitely restricted clones might be of great help in the class II typing of antigen‐presenting cells. Their specific activity was stable for several months. This has allowed the study of some functional properties of these long‐term‐cultured cloned cell lines: interleukin 2 sensitivity and production, helper function in specific antibody synthesis and ability to stimulate in mixed leukocyte reactions.
Pecking order among tumor‐specific antigens
Authors: Urban James L. , van Waes Carter , Schreiber Hans
Published: February 2007

The ultraviolet light‐induced fibrosarcoma 1591 is regularly rejected upon transplantation into young syngeneic mice; in rare instances, however, this tumor grows progressively and the tumors that develop are then heritably stable variant progressor tumors (1591‐PRO tumors). In this study, we have induced transplantation resistance to 1591‐PRO tumors and determined which antigens were recognized by mice that rejected these progressor tumors. We found that cytolytic T cells of such mice recognized a 1591‐specific antigen that was present not only on all the independently derived 1591‐PRO tumors but also on the parental regressor tumor (1591‐RE). However, the cytolytic immune response of mice that rejected 1591‐RE lysed 1591‐RE tumor cells but not 1591‐PRO tumor cells. Thus, the 1591‐RE tumor seemed to express two antigens that were specific for tumors of the 1591 lineage, one that was lost and a second that was retained by 1591‐PRO tumor cells. Mice challenged with 1591‐RE tumor cells mounted a response to only one of the tumor‐specific antigens which was therefore “immunodominant” over the other “immunorecessive” antigen. This immunorecessive antigen became the target of the immune response once the immunodominant antigen was lost. This “pecking order” interfered with the simultaneous recognition of two tumor‐specific antigens and this mechanism may favor immune escape.
Acetylcholinesterase of Schistosoma mansoni: antigenic cross‐reactivity with Electrophorus electricus and its functional implications
Authors: Tarrab‐Hazdai Rebecca , Levi‐Schaffer Francesca , Smolarsky Moshe , Arnon Ruth
Published: February 2007

Acetylcholinesterase (AChE) of the parasite Schistosoma mansoni cross‐reacts with rabbit antibodies against AChE from the electric eel. Cross‐reactivity was demonstrated by radioimmunoassay with sonicate, as well as soluble, preparations from various stages of the parasite life cycle. On sucrose density gradient, the parasite enzyme migrates as an 7.5 S form, whereas an 9.5 S peak is observed with the enzyme‐antibody complex. Immunofluorescence microscopy shows specific staining of intact schistosomula as well as of adult worms. Moreover, the interaction of these antibodies resulted in a marked complement‐dependent cytotoxicity towards intact schistosomula, indicating that AChE is an antigen of significance on the surface of the parasite.
B lymphocyte activation upon exclusive recognition of major histocompatibility antigens by T helper cells
Authors: Pobor Grgur , Pettersson Sven , Bandeira Antonio , Martinez‐A. Carlos , Coutinho Antonio
Published: February 2007

This study has investigated whether exclusive recognition of I‐A or I‐E molecules on the B cell surface by T helper cells is sufficient to activate resting B cells. Lines and clones of long‐term‐cultured T helper cells with specificity for I‐A or I‐E antigens have been derived from mixed lymphocyte cultures between spleen cells from major histocompatibility complex (MHC)‐congenic mouse strains. These cells were tested for helper activity and proved competent to induce resting B lymphocytes expressing the specific MHC antigens to polyclonal expansion and maturation to Ig secretion. B cell activation was shown to require direct recognition of I‐A/E antigens by the helper cells on the responding B lymphocyte surface and it could not be achieved by soluble factors released by “third‐party” helper cell activity ongoing in the same cultures. Since B lymphocyte activation occurs in the absence of antigen recognition by the responding B cells, these observations suggest that I‐A and I‐E molecules expressed on the B cell surface participate in the functional reception of T helper cell‐derived induction signals.
Identification of an anti‐monocyte monoclonal antibody that is specific for membrane complement receptor type one (CR1)
Authors: Hogg Nancy , Ross Gordon D. , Jones David B. , Slusarenko Margaret , Walport Mark J. , Lachmann Peter J.
Published: February 2007

A monoclonal antibody (E11) was produced by immunization of mice with intact human cells of monocyte lineage. Despite the finding that E11 did not inhibit rosettes with C3b‐coated sheep erythrocytes (EC3b), several lines of evidence indicated that E11 was specific for complement receptor type one (CR1). All monocytes, neutrophils, lymphocytes and erythrocytes that reacted with E11 formed EC3b rosettes. The E11 antigen on these cells was shown to be a molecule of 222 × 10 kDa. Treatment of lymphocytes, monocytes, and neutrophils with E11 followed by fluorescein‐coupled F(ab′)2 anti‐mouse‐IgG at 37 °C in buffer lacking sodium azide, led to capping or apparent endocytosis of the E11 antigen and a diminution in CR1 activity of 88%, 59% and 25%, respectively. This same treatment had no detectable effect on monocyte or neutrophil CR3 activity (EC3bi rosettes). Furthermore, with E11‐capped lymphocytes, the residual EC3b rosetting was capped directly over the E11‐fluorescence cap, whereas EC3d, g rosetting (CR2 specific) was undiminished and distributed evenly around the circumference of cells containing E11‐fluorescence caps. Finally, the binding of E11 to cells was inhibited by the prior treatment of these cells with a well characterized rabbit polyclonal anti‐CR1. These data indicated that E11 was specific for a site in CR1 that was distal from the C3b‐binding site, so that E11 was unable to block CR1 activity. E11 proved to be useful for identifying CR1 on various cells in tissue sections, and for quantitating CR1 on erythrocytes and neutrophils. Erythrocytes and neutrophils from normal individuals were found to bind an average of 610 and 4.6 × 104 125I‐labeled E11 molecules per cell. When E11 was visualized in tissues by immunoperoxidase staining, the cells that apparently contained the greatest amounts of CR1 were dendritic reticulum cells and kidney podocytes. The E11 reactive dentritic reticulum cells were characteristic of both follicular and diffuse follicular center cell tumors. Lymphocytes from patients with chronic lymphocytic leukemia (CLL) characteristically expressed little E11, confirming earlier studies that CLL cells lacked CR1 activity detected by EACI‐3b rosette formation. Because normal B cells have been shown to express CR1 at a very early stage of maturation, the absence of CR1 on CLL cells is discordant with the immature nature of CLL cells defined by immunoglobulin expression.
MRC OX‐19: A monoclonal antibody that labels rat T lymphocytes and augments in vitro proliferative responses
Authors: Dallman Margaret J. , Thomas Matthew L. , Green Jon R.
Published: February 2007

A mouse monoclonal antibody, designated MRC OX‐19, has been prepared that binds to virtually all rat thymocytes, T lymphocytes and a maximum of 2% B lymphocytes. Immunoperoxidase studies on tissue sections showed no reactivity with nonlymphoid cells in intestine, thymus, spleen and lymph node. The antigen recognized by MRC OX‐19 antibody was identified by metabolic and cell surface labeling of thymocytes followed by immunoprecipitation and sodium dodecyl sulfate gel elec‐trophoresis. It is a surface glycoprotein of Mr = 69000. When included in in vitro assays for T cell functions, MRC OX‐19 increased proliferation stimulated by allogeneic spleen cells or the lectins phytohemagglutinin and concanavalin A. The antibody itself was not mitogenic and its stimulatory effect could be correlated with an increase in interleukin 2 production. Taken together the data suggest that MRC OX‐19 could be the equivalent of mouse Ly‐1 antigen and human T1 antigen.