bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the interleukin 5‐reactive splenic B cell population
Authors: Rolink Antonius G. , Thalmann Philipp , Kikuchi Yuji , Erdei Anna 
Published: March 2007

AbstractThe characteristics of the interleukin (IL) 5‐reactive splenic B cell population of C57BL/6 nu/nu mice, with respect to IL5/IL2 reactivity, cell surface phenotype, VH gene family usage, autoreactivity and the structure of the IL5 receptor (IL 5R), were analyzed.It was found that 2%–4% of splenic B cells express relatively high levels of IL 5R as determined by the binding of the anti‐IL 5R monoclonal antibody R52.120. Over 90% of the splenic B cells that mature to IgM secretion upon activation with IL5 are comprised in this small subpopulation of B cells. Moreover, the vast majority of splenic B cells that mature to IgM‐secreting cells when activated by IL2 also reside in this IL 5R+ B cell population. The cell surface phenotype of the IL 5R+ splenic B cells is IgM+, B220+, Ly‐1− and IL 2R p55−. Upon activation with IL 5 this cell surface phenotype changes, in that a vast majority of the B cells then express the p55 chain of the IL 2R, whereas the level of IL 5R decreases. VH gene family usage in the IL5‐activated splenic B cells was analyzed by in situ hybridization. VH gene family usage was found to be random and not different from the VH genes expressed in LPS‐activated B cells.Hybridoma collections from IL5‐activated splenic B cells and LPS‐activated B cells were screened and compared for the production of autoantibodies and antibodies directed against the haptens (4‐hydroxy‐3‐iodo‐5‐nitrophenyl)acetyl (NIP) and 2,4,6‐trinitrophenyl (TNP). In both collections high, but not significantly different frequencies of autoantibody‐(32% IL5, 31.4% LPS) and of anti‐hapten antibody (27.8% IL5, 18.6% LPS)‐producing hybridomas were found.The structure of the IL 5R on IL5‐activated B cells was analyzed by 125I‐labeled IL5 binding and cross‐linking. About 100 high‐affinity (10−11 M) and 1000 low‐affinity M IL5‐binding sites are present on IL5‐activated splenic B cells, and both high‐ and low‐affinity IL 5R are similar to those expressed on the IL5‐dependent B13 cell line. Cross‐linking of 125I‐labeled IL5 to the receptors on IL5‐activated B cells revealed one major IL5‐binding protein of 45–50 kDa molecular mass and another minor binding protein of 130–140 kDa. The same IL5‐binding proteins are present on the IL5‐dependent B13 cell line. Thus, we conclude that the structure of the IL 5R on splenic B cells is identical to that on the IL5‐dependent B13 cell line, the IL5R+ splenic B cell population does not differ from the vast majority of the rest of the splenic B cell pool with respect to surface phenotypes (except for expressing IL 5R), VH gene family utilization and autoreactivity.
Stimulation of cloned human T lymphocytes via the CD3 or CD28 molecules induces enhancement in vascular endothelial permeability to macromolecules with participation of type‐1 and type‐2 intercellular adhesion pathways
Authors: Damle Nitin K. , Doyle Laura V. 
Published: March 2007

AbstractPerivascular accumulation of CD29+CD45R0+ memory T lymphocytes at sites of chronic inflammation such as rheumatoid synovium is commonly associated with the localized increase in the endothelial permeability. We have recently demon strated that a direct interaction between activated CD29+CD45R0+ memory T lymphocytes and vascular endothelial cells (EC) results in the increased permeability of EC. In this report, we have investigated effects on antigen‐specific T cell receptor (TcR) α/β+ human T lymphocyte clones on the endothelial permeability to albumin. Our results show that CD29+CD45R0+ cloned human T lymphocytes augment endothelial permeability by a noncytolytic process requiring surface contact between T lymphocytes and EC. Both cytolytic and noncytolytic cloned T lymphocytes were capable of augmenting endothelial permeability and this process did not involve active lysis of EC. Stimulation of T lymphocytes via the CD3/TcR or CD28 molecules resulted in significant enhancement in the ability of T lymphocytes to influence endothelial permeability. Pretreatment of T lymphocytes with monoclonal antibodies directed at either CD11a/CD18 (LFA‐1) or CD2 molecules or that of EC with monoclonal antibodies directed at either CD54 (ICAM‐1) or CD58 (LFA‐3) molecules significantly inhibited T lymphocyte‐induced enhancement in endothelial permeability, thus indicating that activated T lymphocytes utilize both type‐1 (CD11a/CD18CD54) and type‐2 (CD2CD58) intercellular adhesion pathways to augment endothelial permeability and signals received via CD3 or CD28 molecules on T lymphocytes further enhance this process. Furthermore, proinflammatory cytokines interleukin 1 and tumor necrosis factor but not interleukin 6 induced resistance in EC to T lymphocyte‐mediated effects on their permeability. Collectively, these observations may provide insights into molecular mechanism(s) underlying pathophysiology of localized chronic inflammatory responses in general and more specifically selective accumulation of chronically activated memory T lymphocytes at sites of chronic inflammation.
Intravascular metabolism of normal and mutant mouse immunoglobulin molecules
Authors: Pollock Roberta R. , French Deborah L. , Metlay Joshua P. , Birshtein Barbara K. , Scharff Matthew D. 
Published: March 2007

AbstractThe metabolism of IgG immunoglobulins in the body is tightly regulated in order to maintain their intravascular concentration. Different subclasses may have different intravascular half‐lives, and in the mouse, passively administered IgG2b disappears from the circulation more rapidly than IgG2a. We have attempted to localize the sequences in the constant region which are responsible for this difference by examining the intravascular metabolism of mutant immunoglobulins that were generated in tissue culture and have undergone deletions of individual constant region domains or contain different combinations of γ2b and γ2a CH2 and CH3 domains. Our results suggest that the regulation of intravascular metabolism is complex but indicate that sequences in the CH3 domain are important in determining the different intravascular half‐lives of IgG2b and IgG2a antibodies in the mouse.
Infection of Epstein‐Barr virus‐transformed lymphoblastoid B cells by the human immunodeficiency virus: evidence for a persistent and productive infection leading to B cell phenotypic changes
Authors: De Rossi Anita , Roncella Silvio , Calabro Maria Luisa , D'Andrea Emma , Pasti Marcella , Panozzo Marina , Mammano Fabrizio , Ferrarini Manlio , Chieco‐Bianchi Luigi 
Published: March 2007

AbstractFour Epstein‐Barr virus‐positive lymphoblastoid cell lines (LCL) were successfully infected in vitro with immunodeficiency virus type 1 (HIV‐1) as demonstrated by reverse transcriptase activity and p24 HIV antigen in culture supernatants, positive cell staining for gag‐encoded HIV proteins, presence of viral HIV genome by Southern blot analysis and ulstrastructural observations. In addition, both HIV‐1‐infected B cells and their supernatants efficiently transactivated the chloramphenicol acetyl transferase reporter gene which is under the control of the HIV‐1 long terminal repeat.The LCL cells displayed long‐term HIV‐1 infection and production, but no cytopathic effects were observed. Cytofluorimetric analysis did not detect membrane CD4 presence in the LCL cells before and after HIV‐1 infection; moreover, a minute amount of CD4 mRNA was observed only in one of the LCL. A monoclonal antibody specific for the viral binding site of the CD4 molecule delayed, but did not block, HIV‐1 infection of the LCL cells.Following HIV‐1 infection, changes in LCL phenotype were observed, consisting of a decrease in CD23‐ and CD39‐positive cells, and a concomitant increase of cells with surface CD10 and Bac‐1. Furthermore, HIV‐1‐infected LCL cells did not grow in tight clumps, as usually observed in uninfected LCL, but as disperse suspensions, and formed more agar colonies than control LCL. However, despite this apparent acquisition of a malignant‐like phenotype, c‐myc proto‐oncogene rearrangement was not detected. The appearance of cells with new characteristics did not seem due to clone selection by HIV‐1 infection, since all the LCL conserved their clonotypic pattern of IgH chain rearrangement.The acquisition of malignant‐like features by HIV‐infected B cells might be clinically significant in terms of the pathogenesis of non‐Hodgkin's B cell lymphomas, which occur frequently in AIDS patients.
Bone marrow transplantation from mutant lpr/lpr mice. Functional abnormalities rather than alloantigenic differences appear to determine the development of a graft‐vs. ‐host‐like syndrome
Authors: Allen Ruth D. , Marshall Jan D. , Roths John B. , Sidman Charles L. 
Published: March 2007

AbstractTransfer of bone marrow (BM) from autoimmunity‐prone mice homozygous for the lymphoproliferation (lpr) mutation to irradiated congenic +/+ recipients has previously been shown to result in a syndrome similar to chronic graft‐vs.‐host (GVH) disease. It has been suggested that this syndrome may be due to an antigenic difference caused by the lpr mutation itself or to antigenic differences at loci closely linked to the lpr locus (Theofilopoulos, A. N. et al., J. Exp. Med. 1985. 162: 1; Mosbach‐Ozmen, L. and Loor, F., Thymus 1987. 9: 197). However, the results presented here indicate that alloantigenic differences do not play a role in this syndrome. Instead, the chronic disease observed in lpr/lpr→+/+ BM chimeras appears to develop as a result of a functional defect associated with the lpr mutation which is expressed shortly after transfer of lpr/lpr BM to irradiated recipients. This defect causes an increase in the levels of serum IgG1 and IgG2, which peak at 4–5 weeks post‐transfer and then decline to normal levels by 9–10 weeks post‐transfer. Inflammation similar to that observed in classic GVH reactions accompanies excess IgG production in congenic +/+ recipients but not in lpr/lpr recipients of lpr/lpr BM. We demonstrate that the GVH‐like response occurring in lpr/lpr→+/+ chimeras is dependent on mature T cells, but that either lpr/lpr or +/+ T cells can support this reaction. These results suggest that transfer of lpr/lpr BM to normal mice causes immunoregulatory disturbances which lead to nonspecific activation of T cells. We speculate that lpr/lpr BM causes a GVH‐like reaction in +/+ recipients but a systemic lupus erythematosus‐like syndrome in lpr/lpr recipients because of intrinsic differences in the +/+ and lpr/lpr host environments. Considering these findings, the lpr/lpr→+/+ GVH model may be useful for analysis of factors capable of inducing undesirable reactions in clinical BM transplantation between nominally histocompatible donors and recipients, in addition to being informative about the nature of the lpr mutation itself.
Tolerance to experimental contact sensitivity induced by T cell vaccination
Authors: Mekori Yoseph A. , Karin Nathan , Gottesman Giora , Cohen Irun R. 
Published: March 2007

AbstractIt was shown previously that experimental autoimmune diseases could be prevented or treated specifically by administering suitably attenuated autoimmune T lymphocytes to animals, a process termed T cell vaccination (Cohen, I. R., Sci. American 1988. 256: 52). We now report that T cell vaccination is an effective way of inducing tolerance to contact sensitivity to simple chemical haptens. Vaccines were prepared from populations of lymph node cells from specifically sensitized mice by activating the T cells with the T cell mitogen concanavalin A and then treating the T cell blasts with glutaraldehyde. The vaccinated mice showed decreased delayed sensitivity responses to the specific sensitizing antigen and developed significant delayed sensitivity responses to the T cells of the same specificity as those used for vaccination. Thus, T cell vaccination against contact sensitivity reactions appears to function similarly to T cell vaccination against autoimmune disease.
Analysis of the T cell repertoire for myelin basic protein in thymus‐grafted and other types of chimera: evidence that major histocompatibility complex molecules on accessory cells rather than T cell specificity mainly regulate susceptibility to autoimmune encephalomyelitis
Authors: Matsumoto Yoh , Kawai Kazuhiro , Fujiwara Michio 
Published: March 2007

AbstractExperimental autoimmune encephalomyelitis (EAE) is a T cell‐mediated autoimmune disease inducible in rodents by immunization of brain‐specific antigens such as myelin basic protein (MBP). It is also well known that various strains of rats differ in their susceptibility to EAE upon active immunization. To elucidate the immune mechanisms of susceptibility and resistance to EAE, we first examined the T cell repertoire for MBP using thymectomized chimeras that possessed thymuses from EAE‐susceptible (LEW) or EAE‐resistant (BM) strains. It was revealed that T cell specificity of these chimeras was skewed toward that of the grafted thymus. Very interestingly, the chimeras bearing thymuses from the resistant strain developed severe EAE, keeping a hole in the encephalitogenic 68‐88 sequence of MBP. These findings suggest that the strain‐specific T cell repertoire itself is not involved in the regulation of EAE susceptibility. Furthermore, the analysis of the chimeras reconstituted with F1 T cells and marrow cells from various strains indicates that the major histocompatibility complex (MHC) molecules expressed on accessory cells primarily determine susceptibility or resistance to EAE. We finally showed, using various inbred and congenic rats carrying RT1l or RT1n, that susceptibility to EAE of rats carrying RT1l is heavily influenced by the background genes, whereas resistance to EAE of rats carrying RT1n is primarily regulated by the MHC molecules expressed on accessory cells without influence of the background genes.
Structures on the I‐A molecule predisposing for susceptibility to type II collagen‐induced autoimmune arthritis
Authors: Gustafsson Kenth , Karlsson Mikael , Andersson Leif , Holmdahl Rikard 
Published: March 2007

AbstractThe susceptibility to type II collagen (CII)‐induced arthritis (CIA) in mice is profoundly influenced by major histocompatibility complex (MHC) class II genes in the H‐2 region. Analyses of MHC‐congenic strains on the B10 background show that only strains developing an anti‐CII antibody response after immunization with autologous CII develop arthritis after induction with CII from various species. The susceptible haplotypes have been found to be H‐2q, H‐2r, H‐2w3 and H‐2w17. In addition, these haplotypes respond to different patterns of CII derived from various species suggesting that T cell receptors and CII peptides interact. In contrast, certain haplotypes closely related to H‐2q, such as the H‐2p and H‐2w5 haplotypes, are resistant to induction of CIA and are nonresponders to CII. We have earlier shown that a critical structure on the I‐Aβ molecule determines the susceptibility differences between the p and q haplotypes. We have now determined the structure of exon 2 of the Aβ as well as some of the Aα genes of the remaining haplotypes in the p, q and r families. The sequences show similarities between the CIA‐susceptible haplotypes in the Aβ C‐terminal part and the Aα N‐terminal part of the first domains forming a large part of the antigenic peptide‐binding site. Among the wild mouse‐derived haplotypes, the w5 haplotype showed an Aβ sequence identical to that of the p haplotype consistent with its nonresponder nature to CII immunization. These findings suggest that (a) structures shared between different class II molecules are of importance for the susceptibility to disease in mouse strains and (b) most likely recognition of different CII peptides is important for development of disease.
Critical role of an amino acid residue in a T cell determinant is due to its interaction with a neighboring non‐critical residue
Authors: Boyer Michel , Novak Zuzana , Fotedar Arun , Fraga Ester , Singh Bhagirath 
Published: March 2007

AbstractSeveral lines of evidence support the concept of two functionally distinct sites on antigen: the epitope, involved in interaction with the T cell receptor and the agretope, interacting with Ia. We investigated the Ia and T cell receptor interaction sites on the synthetic polypeptide antigen poly‐18 [poly‐EYK(EYA)5] using T cell hybridoma clones specific for this antigen in the context of I‐Ad. Peptides with amino acid sequences related to poly‐18 were synthesized. These were used to identify the critical residues in the minimum peptide sequence required for activation. Clone A.1.1 responds to the minimal peptide EYK(EYA)4 but not to (EYA)5. This identifies Lys3 as a critical amino acid for this hybridoma. Surprisingly, the substituted peptide EYAEAA(EYA)3 could activate A.1.1, indicating that an Ala at position 5 instead of a Tyr obviates the critical requirement for Lys3. This demonstrates that the function of critical residues may extend beyond contacting the T cell receptor or Ia, to include a third role: that of interacting with other amino acids of the T cell epitope, thus influencing the antigen's recognition by T cells.
γ/δ T cells and α/β T cells differ in their developmental patterns of receptor expression and modulation requirements
Authors: George James F. , Cooper Max D. 
Published: March 2007

AbstractMeasurement of the cell surface levels of γ/δ (TcR1) and α/β (TcR2) T cell receptors in the chicken revealed that thymocyte subpopulations that express these receptor isotypes differ remarkably in their rates of receptor acquisition. Whereas TcR 1 expression was relatively high (> 104 sites per cell) beginning on day 12 of embryonic life, the initial levels of TcR2 expression on embryonic thymocytes were relatively low (approximately 103 sites per cell) when first measurable on day 15, and increased gradually as a function of T cell maturation. In peripheral tissues, the TcR 1 cells also expressed higher receptor levels than did the TcR 2 cells, but the difference was only 2–3‐fold. The TcR 2 receptors on immature T cells could be easily modulated by receptor cross‐linkage, very much like immunoglobulin receptors on immature B cells. While the TcR 2 receptor modulation occurred within minutes, TcR 1 receptor modulation required several hours for completion, even in the embryonic thymus. The data indicate very different developmental programs for TcR 1 and TcR 2 expression, and suggest fundamental differences in clonal selection modes for the two T cell subpopulations.
Presentation of endogenous immunoglobulin determinant to immunoglobulin‐recognizing T cell clones by the thymic cells
Authors: Rudensky Alexander Y. , Mazel Svetlana M. , Yurin Vitalij L. 
Published: March 2007

AbstractUsing immunoglobulin (Ig)‐recognizing T helper clones the expression of Ig peptide/major histocompatibility complex class II complexes derived by the processing of endogeneous Ig molecules in the thymus was demonstrated. It was found that thymic B cells but not “classic” thymic antigen‐presenting cells and macrophages represent the major antigen‐presenting cell type of determinants of endogenously synthesized surface Ig (Igx‐1b) and anti‐surface Ig antibodies (IdC3B9). The Igx‐1b‐presenting activity in the thymus appears relatively late, only after 3 weeks of postnatal life, while in the spleen an efficient presentation of endogenous Igx‐1b epitope is observed very early after birth. This difference between thymic and peripheral presentation of endogeneous Ig determinant could be important for understanding the mechanisms of T cell tolerance to self Ig and the role of self Ig in negative and positive selection of T cell repertoire.
Characterization of an IgA receptor from group B streptococci: specificity for serum IgA
Authors: Lindahl Gunnar , Åkerström Bo , Vaerman Jean‐Pierre , Stenberg Lars 
Published: March 2007

AbstractSome strains of group B streptococci express a cell surface protein which binds IgA. This report describes some properties of such an IgA receptor and compares it with a previously described IgA receptor from group A streptococci. The group B receptor was released in an almost pure form from bacteria incubated at elevated pH, and could be isolated by IgA‐Sepharose affinity chromatography. The sequence of the N‐terminal 19 amino acid residues was unique. The receptor preferentially binds IgA of human origin, as shown in immunoblotting experiments with purified IgA from nine different species. The affinity constant of the purified receptor for serum IgA was determined to be 3.5 × 108 M−1, but for secretory IgA it was too low to allow determination. This result indicates that secretory component and/or J chain interferes with the binding of IgA to this type of bacterial receptor, which may be one of the physiological functions of these polypeptides. A reduction in affinity was also observed for another complexed form of IgA, α1‐microglobulin‐IgA. The group B receptor is antigenically unrelated to the IgA receptor from group A streptococci (protein Arp), but competitive inhibition experiments indicate that they bind to the same region in IgA. The implications of these findings, and the biological role of bacterial IgA receptors, are discussed.
Expression of the Epstein‐Barr virus (EBV)‐encoded membrane antigen (LMP) increases the stimulatory capacity of EBV‐negative B lymphoma lines in allogeneic mixed lymphocyte cultures
Authors: Cuomo Laura , Trivedi Pankaj , Wang Fred , Winberg Gösta , Klein George , Masucci Maria G. 
Published: March 2007

AbstractEpstein‐Barr virus (EBV)‐negative Burkitt lymphoma (BL) lines are poor stimulators in allogeneic mixed lymphocyte cultures compared to EBV‐transformed lymphoblastoid cell lines derived from the same individuals. We have previously shown that the stimulatory capacity of the tumor cells is increased after EBV conversion (Avila‐Carino et al., Int. J. Cancer 1987. 40: 691). As a first step towards the identification of the viral gene product responsible for this change we have studied the influence of the EBV latent membrane protein (LMP) on the stimulatory capacity of the EBV‐negative BL lines BL41 and DG75 and the B lymphoma line BJAB.Four LMP‐transfected sublines of BL41, four DG75 LMP transfectants and one LMP‐transfected subline of BJAB showed a significantly stronger stimulatory capacity than the original line. The effect was directly proportional to the amount of LMP detected in each transfectant but was not due to reactivation of LMP‐specific memory cells since lymphocytes from EBV‐seropositive and ‐seronegative individuals responded equally. In order to define the relation between LMP expression and induction of stimulatory capacity, DG75 was transfected with constructs containing the LMP gene under the control of an heat‐shock promoter. The peak of LMP expression in heat shock‐treated cells preceded the appearance of stimulatory capacity by 6–12 h suggesting that critical amounts of the protein may be required to induce the phenotypic change recognized by the T cells.LMP influenced in a dose‐dependent manner the expression of the adhesion molecules LFA‐1, LFA‐3 and ICAM‐1 and B cell activation markers CD23 and CD39 in transfected sublines of BL41, but did not affect the expression of these markers in the DG75 and BJAB cell line. All LMP‐expressing transfectants showed an increased capacity to form conjugates with unprimed allogeneic lymphocytes.