bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naturally acquired antibody responses to the components of the Plasmodium falciparum merozoite surface protein 1 complex
Authors: Wang Lina , Crouch Lucy , Richie Thomas L. , Nhan Doan Hanh , Coppel Ross L. 
Published: December 2003

SUMMARY Merozoite surface protein 6 (MSP6) and 7 (MSP7) of Plasmodium falciparum are peripheral membrane proteins whose cleaved products, MSP636, MSP722 and MSP719, are found on the merozoite surface as components of a non‐covalently bound complex which also contains four polypeptides derived from merozoite surface protein 1 (MSP1). We have expressed both the precursor regions and the processed mature products of MSP6 and MSP7 in Escherichia coli and showed that these recombinant proteins react with human immune sera. In a set of sera collected from individuals living in malaria‐endemic areas of Southern‐central Vietnam, antibodies to the mature polypeptides of MSP636 and MSP722 were detected in 50·6 and 85·6% of the serum samples, whereas antibodies to the precursor regions of MSP6 and MSP7 were detected in only 12·1 and 42·5% of the serum samples, respectively. The predominant subclass of anti‐MSP6 antibodies was IgG1, whereas the predominant subclass of anti‐MSP7 antibodies was IgG3. In the same set of serum samples, the antibody responses to MSP119 are predominantly IgGI, whereas antibodies to merozoite surface protein 4 (MSP4) are mainly IgG3. This data is consistent with the proposition that, during malaria infection, variable proteins induce responses that are predominantly of the IgG3 isotype, and conserved proteins induce responses that are predominantly IgG1. The antibodies to MSP6, MSP7 and MSP119 all decreased at the time of infection, but increased during the convalescent period. No correlation was observed between the antibodies at the commencement of the study and absence of parasitaemia during surveillance in this population.
Local skin reaction (chancre) induced following inoculation of metacyclic trypanosomes in cattle by tsetse flies is dependent on CD4 T lymphocytes
Authors: Naessens Jan , Mwangi Duncan M. , Buza Joram , Moloo Shamshudeen K. 
Published: December 2003

SUMMARY The first visible response in livestock to the bite of a trypanosome‐infected tsetse fly is the formation of a localized skin reaction, also known as a chancre. This is an inflammatory response in the skin associated with swelling and an influx of cells. It is thought to be associated with an acquired immune response to the injected metacyclic trypanosomes. In this study, we examined the role of T lymphocytes in the development of the inflammatory response, by depleting cattle of T cell subpopulations and monitoring the development of chancres. Depletion of CD4 cells, but not CD8 cells, resulted in a significant reduction in chancre formation, confirming that an acquired response mediates the inflammatory response. In addition, it was established that the CD4 T cells mediate the generation of memory for immunity to a homologueous re‐challenge. The inflammatory response in the skin did not affect further progress of the infection.
A DNA‐prime/protein‐boost vaccination regimen enhances Th2 immune responses but not protection following Schistosoma mansoni infection
Authors: DA’Dara Akram A. , Skelly Patrick J. , Walker Christine M. , Harn Donald A. 
Published: December 2003

SUMMARY DNA immunization represents a promising vaccine strategy that has been reasonably successful, and will likely play an even greater role in vaccine development as these vaccines continue to be improved. We have developed a partially protective DNA vaccine against schistosome infection based on a 23‐kDa integral membrane protein, Sm23. The focus of this study was to compare immunogenicity and efficacy of vaccination regimens utilizing Sm23 DNA vaccine alone vs. regimens that utilized both Sm23 DNA and Sm23 in recombinant protein form. We found that priming and boosting with the Sm23 DNA construct (Sm23‐pcDNA) resulted in a significant level of protection against challenge infection (36–44%). In contrast, altering this protocol by changing the boost from Sm23 DNA to boosting with recombinant Sm23 protein (rSm23) formulated in aluminium hydroxide (alum) failed to induce a significant reduction in worm burdens. Similarly, mice primed and boosted with the rSm23 in alum also did not develop significant levels of protection against challenge infection. We hypothesize that the differences in the ability to drive protective immunity using the DNA prime‐DNA boost strategy and the inability to do so when recombinant Sm23 in alum was substituted for Sm23 DNA is due to driving of different immune responses. In support of this, we found that mice primed and boosted with Sm23‐pcDNA had Th1‐type immune responses characterized by low anti‐Sm23 IgG1 : IgG2a antibody isotype ratios, whereas mice boosted with rSm23 had higher IgG1 : IgG2a ratios. In addition, priming and boosting with rSm23 elicited mainly IgG1 antibodies with no detectable IgG2a, indicative of a polarized Th2‐type immune response. Thus, similar to our earlier work, the results of this study show that protective vaccination using Sm23 is associated with a Th1 immune response, and efficacy is diminished using protocols that diminish this Th1 bias. In our study, this was likely due to the use of the Th2‐driving adjuvant alum, and future studies are planned where we will compare the protective efficacy of rSm23 administered with Th1‐type adjuvants.
In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface antigens associated with severe malaria in African children
Authors: Staalsoe Trine , Nielsen Morten A. , Vestergaard Lasse S. , Jensen Anja T. R. , Theander Thor G. , Hviid Lars 
Published: December 2003

SUMMARYP. falciparum‐infected red blood cells (IRBC) can adhere to endothelial host receptors through parasite‐encoded, clonally variant surface antigens (VSA). The VSA‐mediated IRBC adhesion and the acquired VSA‐specific antibody response have both been linked to IRBC organ tropism and disease severity. Parasites isolated from young children with severe malaria (SM) tend to express a limited and conserved set of VSA (VSASM) that are both stronger and more commonly recognized by IgG in the plasma of malaria‐exposed individuals than VSA (VSAUM) expressed by parasites causing uncomplicated malaria (UM) in older semi‐immune children. Establishment of the genetic mechanism underlying changes in VSA expression in response to in vitro selective pressure is now possible because of the availability of the entire genomic sequence of the P. falciparum clone 3D7. As a first step towards direct molecular identification of VSASM‐encoding genes in 3D7, we report here a method of enforcing expression of VSASM‐like antigens in this parasite clone by a novel selection method using plasma from semi‐immune children with low VSAUM‐specific, but high VSASM‐specific, IgG reactivity. In addition to the resulting increase in VSA‐specific IgG recognition, VSASM‐expressing 3D7(3D7‐Dodowa1) showed reduced adhesion to CD36. Finally, levels of IgG specific for the VSA expressed by 3D7‐Dodowa1 were uniformly higher than those of IgG with specificity for VSA expressed by the unselected 3D7 in plasma samples from geographically and epidemiologically diverse areas of endemic parasite transmission. The described selection method appears a useful tool in the identification of genes encoding VSA involved in severe and life‐threatening P. falciparum malaria.
Humoral immune responses induced by Kudoa sp. (Myxosporea: Multivalvulida) in BALB/c mice: oral administration, immunization and cross‐reactions with Myxobolus aeglefini (Myxosporea: Bivalvulida)
Authors: Martínez De Velasco Gonzalo , Cuéllar Carmen 
Published: December 2003

SUMMARY The majority of Kudoa species infect the somatic muscle of fish, establishing cysts. Because there is no effective method to detect infected fish without destroying them, these parasitized fish reach the consumer. The elevated humoral responses detected previously by us in BALB/c mice immunized with Kudoa sp. pseudocyst extracts showed the possible immunopathological effects in man from the ingestion of Kudoa‐infected fish. In this work, the high IgG1 and IgE levels induced by the oral administration of Kudoa pseudocysts to BALB/c mice confirmed the allergenic nature of some of their components. An alternative way of preparing the soluble extract by using a FastPrep‘ shaker indicated the inconvenience of using sonication to prepare the Kudoa sp. extract. IgG+M, IgG, IgG3 and IgA cross‐reactions of Kudoa sp. with another myxosporean, Myxobolus aeglefini, were found.
Adrenocortical hormones and interleukin patterns in leprosy
Authors: Leal Ângela M. O. , Magalhães Patrícia K. R. , Souza Cacilda S. , Foss Norma T. 
Published: December 2003

SUMMARY The functional status of adrenocortical hormones and their relationship to the pattern of inflammatory cytokines in the lepromatous and tuberculoid poles of leprosy were investigated. Interleukin (IL)‐1β, IL‐6 and tumour necrosis factor (TNF)‐α plasma levels, C‐reactive protein (CRP) concentrations and erythrocyte sedimentation rates (ESR) were significantly higher in LL/BL (lepromatous) leprosy patients than in control subjects. There was a significant positive correlation between IL‐6 and TNF‐α plasma levels and ESR and CRP concentrations. IL‐1β was positively correlated with ESR but not with CRP. Both baseline and stimulated adrenocorticotropic hormone and cortisol plasma levels were not different between patients and control subjects. In contrast, adrenal androgen dehydroepiandrosterone sulphate (DHEA‐S) plasma levels were significantly lower in leprosy patients than in sex‐matched control subjects. There was a significant inverse correlation between DHEA‐S and IL‐6, TNF‐α, and CRP concentrations. This finding may be of pathogenetic significance in this disease and in other inflammatory states.
Factors influencing Leishmania major infection in IL‐4‐deficient BALB/c mice
Authors: Kropf P. , Herath S. , Weber V. , Modolell M. , Müller I. 
Published: December 2003

SUMMARY The outcome of Leishmania major infection in IL‐4‐deficient BALB/c mice has been a controversial subject. We have shown that IL‐4‐deficient BALB/c mice infected with Leishmania major developed progressive lesions and could not contain the replication of the parasites, whereas other studies have reported that IL‐4‐deficient mice were able to resist infection. Therefore, we examined different factors that can influence the course of Leishmania major infection. We tested different lines of IL‐4‐deficient BALB/c mice and show that the reported differences in the outcome of infection were not due to the different genetic origin of the embryonic stem cells used to disrupt the IL‐4 gene. In addition, we infected IL‐4‐deficient mice with different isolates of L. major parasites and show that none of the parasite strains tested were cleared, although some of them caused milder pathology. Interestingly, this milder pathology was paralleled by a reduced arginase activity of the parasites. We also tested the influence of age on the course of Leishmania major infection in IL‐4‐deficient BALB/c mice and show that older mice express a transient resistance. Thus, we conclude that differences in the age of the mice and in the arginase activity of the different isolates of parasites are factors that can influence the non‐healing phenotype of IL‐4‐/‐ BALB/c mice.
Early B‐lymphocyte precursors and their regulation by sex steroids
Authors: Kincade Paul W. , Medina Kay L. , Payne Kimberly J. , Rossi Maria Isabel D. , Tudor Kim‐Sue R. S. , Yamashita Yoshio , Xx Taku 
Published: December 2003

Summary: This review describes an improved characterization of early B‐lymphocyte precursors in mice and the remarkable sensitivity of the same cells to hormones. The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) was used as a marker to image and characterize bone marrow cells lacking all lineage‐associated markers. Most early TdT+ precursors have a distinctive density of c‐kit and express the interleukin‐7Ra chain, as well as flt‐3/flk2, but lack CD34. An understanding of those cell surface properties made it possible to obtain highly enriched, viable cells with the potential to give rise to CD19+ lymphocytes in culture. A series of other flow cytometry and culture experiments suggested a possible differentiation sequence for these early pro‐B cells. This new model was used to advantage in our studies of sex steroids. It appears that early precursors represent a hormone‐sensitive control point for determining numbers of new B lymphocytes that are produced within bone marrow. We also compare and contrast these findings with B lymphopoiesis in humans.
Transcriptional regulation of early B‐lymphocyte differentiation
Authors: O'Riordan* Mary , Grosschedl** Rudolf 
Published: December 2003

Summary: Differentiation of hematopoietic progenitors into the B‐lymphocyte lineage requires co‐ordination of a complex network of transcriptional regulators. Lineage specificity is likely to result from combinatorial mechanisms of gene regulation. Four general functions are mediated by transcription factors in the differentiating pro‐B cell. First, a cascade of B‐cell‐restricted transcription factors is upregulated. Second, genes involved in the specification of other cell fates are repressed. Both activation and repression require the participation of different classes of transcriptional regulators, including proteins of the Ikaros family that can recruit chromatin‐modifying complexes. Third, the expression of genes that facilitate B‐cell proliferation and differentiation are activated. Lastly, genes required for recombination are expressed and targeted to the immunoglobulin loci, thus initiating the characteristic rearrangement of the immunoglobulin genes. The interactions and functions of transcription factors in pro‐B‐cell differentiation are discussed.
All B cells are progeny of endothelial cells: a new perspective
Authors: Nishikawa Shin‐Ichi , Fraser Stuart , Fujimoto Tetsuhiro , Endoh Mitsuhiro , Nishikawa Satomi , Ogawa Minetaro 
Published: December 2003

Summary: We present here a speculative view of embryonic hematopoiesis. We do this with the hope of finding directions for future study, keeping in mind that our model may diverge from the real situation. However, we want to emphasize that previous models have neglected the possibility that endothelial cells (EC) represent a progenitor of hematopoietic cells (HPC). Emerging evidence, including our own, and previous histological studies argue for the presence of hemogenic EC. We discuss seemingly contradictory points of view of embryonic hematopoiesis, such as the origin of lymphogenic progenitors, and have shown that they may be resolved more satisfactorily by introducing this notion. Obviously, a good model should be a testable one, so we are currently developing experimental systems to demonstrate that all B cells are, indeed, the progeny of EC.
Apoptosis and its modulation during B lymphopoiesis in mouse bone marrow
Authors: Lu Liwei , Osmond Dennis G. 
Published: December 2003

Summary: Studies in normal, gene‐deleted, transgenic and mutant mice have examined apoptotic cell death and its role in B lymphopoiesis in bone marrow. Apoptotic activity has been quantitated among phenotypically defined populations of precursor B cells using flow cytometry of apoptotic cells and an established model of B‐cell development. In normal mice, the frequencies of apoptotic cells (apoptotic index) and accumulation of apop­totic cells during short‐term culture (apoptotic rate) are maximal at around the pro/pre‐B‐cell transition and among immature B lymphocytes. The brief period between onset of apoptosis and clearance by macro­phages (apoptotic transit time) is similar for most precursor B‐cells. Apop­tosis‐modulating factors produce substantial changes in apoptotic activity among pro‐B and pre‐B cells, associated with altered expression of bcl‐2 family proteins. Pro‐B‐cell apoptosis, normally extensive, is markedly suppressed in the absence of p53. Complete pro‐B‐cell abortion in RAG‐2 deletion provides an assay for apoptotic fractions in other experimental systems. Pre‐B‐cell apoptosis is enhanced by deficiencies of interleukin (IL)‐7, Abl protooncogene or colony‐stimulating factor (CSF)‐1 and overexpression of heat‐stable antigen, and is inhibited by IL‐7 and p190bcr/abl transgenes. CSF‐1 and melatonin administration inhibit pre‐B‐cell apoptosis, probably via stromal cell stimulation. Such apoptotic modulation has implications for B‐cell homeostasis, quality control, immunodeficiency and neoplasia.
The chicken B‐cell receptor complex and its role in avian B‐cell development
Authors: Sayegh Camil E. , Demaries Sandra L. , Pike Kelly A. , Friedman Jennifer E. , Ratcliffe Michael J. H. 
Published: December 2003

Summary: The bursa of Fabricius is critical to normal B‐lymphocyte development in birds. During embryonic life, B‐cell precursors migrate to the bursal rudiment and those which have undergone productive V(D)J recombination colonize lymphoid follicles and undergo immunoglobulin V gene diversification by gene conversion. The chicken surface IgM complex appears structurally and functionally equivalent to its mammalian counterpart, with homologs to CD79a and CD79b. Expression of a truncated Ig chain is sufficient to drive the early stages of B‐cell development in the embryo bursa. Bursal cells expressing the truncated receptor complex proliferate in bursal follicles, and those which contain V gene rearrangements undergo V gene diversification by gene conversion. The bursa is a gut‐associated organ and antigen is focused to bursal lymphoid follicles after hatch. While expression of the truncated chain is sufficient to support B‐cell development in the embryo, B cells expressing this receptor are rapidly eliminated after hatch. We suggest the possibility that B‐cell development in the bursa after hatch is driven by encounter with antigen leading to redistribution of B cells within the lymphoid follicle, B‐cell proliferation and V gene repertoire development by gene conversion.
Pre‐B and pre‐T‐cell receptors: conservation of strategies in regulating early lymphocyte development
Authors: Muljo Stefan A , Schlissel Mark S. 
Published: December 2003

Summary: Early lymphocyte development is characterized by the regulated activity of the V(D)J recombinase and the positive and negative selection of cells based on the structure of their assembled antigen receptor genes. Developing B and T cells use remarkably similar signaling complexes, the pre‐B‐cell receptor (pre‐BCR) and the pre‐T‐cell receptor (pre‐TCR) respectively, to monitor the progress of antigen receptor gene assembly. This review will compare and contrast the regulation and activities of the pre‐BCR and pre‐TCR signaling complexes. In addition, we will consider a number of critical but as yet unanswered questions prompted by such an analysis.
Repertoire selection by pre‐B‐cell receptors and B‐cell receptors, and genetic control of B‐cell development from immature to mature B cells
Authors: Melchers Fritz , Ten Boekel Edwin , Seidl Thomas , Kong Xian Chu , Yamagami Tamotsu , Onishi Kazuo , Shimizu Takeyuki , Rolink Antonius G. , Andersson Jan 
Published: December 2003

Summary: During B‐cell development the surrogate light (SL) chain is selectively expressed in progenitor and precursor B cells during the developmental stages of DH to JH and VH to DH JH rearrangements. Approximately half of all H chains produced by these rearrangements cannot pair with SL chains and cannot form a pre‐B‐cell receptor (pre‐BCR). A spectrum of affinities between VpreB and individual VH domains generates preB cells with pre‐BCR of different fitness which, in turn, determines the extent of the pre‐B II‐cell proliferation and the fidelity of allelic exclusion of the H chain locus. Once pre‐BCR is expressed, SL chain expression is turned off. As pre‐B II cells proliferate, SL is diluted out, thus limiting pre‐BCR formation. As a consequence, pre‐B II cells stop proliferating, become small and resting and begin to rearrange the L chain loci. Multiple rearrangements of the k L chain alleles are often detected in wild‐type small pre‐B II cells. Around 20% of the H chain‐expressing small pre‐B II cells also express L chains but do not display the Ig on the surface. Hence, it is likely that not all L chains originally generated in resting pre‐B II cells can pair with the H chain previously present in that cell. The best fitting ones are selected preferentially to generate sIg+ B cells. Furthermore, the transition of immature B cells from the bone marrow to spleen and their development to mature cells appear as two separate steps controlled by different genes.
The role of the preBCR, the interleukin‐7 receptor, and homotypic interactions during B‐cell development
Authors: Stoddart Angela , Fleming Heather E. , Paige Christopher J. 
Published: December 2003

Summary: Considerable progress has been made in defining intermediate stages in the process leading from stem cells to mature B cells. Cell‐bound and secreted molecules direct the progression through these stages and regulate the selection of clones from which the immune repertoire emerges. In fact, a myriad of signals derived from B‐cell progenitors themselves and the microenvironment in which they develop direct the differentiation process. These signals are provided by B‐cell antigen receptors (BCR) and their surrogates, and by adhesion and cytokine receptors. The co‐operation of these receptors to control survival, expansion, and differentiation of early B‐cell progenitors is the topic of this review. Specifically, we will summarize recent findings from our laboratory demonstrating that preBCR expression lowers the threshold for interleukin (IL)‐7 responsiveness. How signals initiated by these receptors may intersect at this critical point of B‐cell selection will be discussed. At the stage following IL‐7 responsiveness we have shown that interactions between B‐cell progenitors themselves promote their differentiation to immunoglobulin‐secreting B cells. We propose that one function of stromal cells, known to be central to B lymphopoiesis, is to promote critical preB–preB homotypic interactions and ensuing signals.
B‐cell subsets and the mature ­preimmune repertoire. Marginal zone and B1 B cells as part of a “natural immune memory”
Authors: Martin Flavius , Kearney John F. 
Published: December 2003

Summary: The rate of elimination of a pathogenic agent is of critical importance for the host and determines the extent and consequences of the infection. Antibody production, along with the activity of other cells of the immune system, plays an important role early and late in the response and contributes to all containment and elimination of the organism. B‐cell clones reaching the mature long‐lived pool are heterogeneous: some belong to the B1 B‐cell subset, some are enriched in the CD21high compartment (mostly marginal zone (MZ)), whereas others recirculate primarily among the B‐cell follicles (FO). This segregation is a T‐independent, CD40L‐independent but BCR/CD19‐dependent process. Antigen encounter will recruit antigen‐specific cells from the pool of mature B‐lymphocytes and activate them to perform effector functions. CD21highCD23low B cells enriched in the MZ of the spleen initiate the early plasmablast wave during the first 3 days of an antibody response against particulate T‐independent bacterial antigens. These findings indicate a functional heterogeneity within the mature B‐lymphocyte population. MZ B cells and B1 B, in contrast to FO B cells, have the unique capacity to generate effector cells in early stages of the immune response against (particulate) antigens that are scavenged efficiently in these specialized anatomical sites.