bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoglobulin isotype regulation by antigen‐presenting cells in vivo
Authors: de Becker Geneviève , Sornasse Thierry , Nabavi Nasrin , Bazin Hervé , Tielemans Françoise , Urbain Jacques , Leo Oberdan , Moser Muriel 
Published: March 2007

AbstractThe isotype and magnitude of the B cell response clearly depends on the in vivo activation of T helper (Th) cells which secrete different lymphokines. Since Th are activated by the presentation of the antigen on specialized cells, we wished to test whether the nature of the antigen‐presenting cells (APC) influences the isotypic profile of the humoral response. Data are presented showing that antigen‐pulsed dendritic cells (DC) and peritoneal macrophages induce the synthesis of specific antibodies when injected in syngeneic animals. By contrast, a single injection of antigen‐pulsed resting B cells does not prime the mice in vivo. Moreover, the injection of antigen‐pulsed DC induces the synthesis of specific IgG2a and IgG1 antibodies, whereas peritoneal macrophages favor the production of IgG1 and IgE antibodies specific for the antigen. These data show that the isotype and the amplitude of the B cell response can be regulated by the nature of the APC, and indirectly suggest that Th cell differentiation is controlled at the level of antigen presentation.
Deletion of T lymphocytes in human CD4 transgenic mice induced by HIV‐gp120 and gp120‐specific antibodies from AIDS patients
Authors: Wang Zhi‐Qin , Orlikowsky Thorsten , Dudhane Anita , Mittler Robert , Blum Michelle , Lacy Elizabeth , Riethmüller Gert , Hoffmann Michael K. 
Published: March 2007

AbstractCD4, a T cell receptor for major histocompatibility complex class II antigen, is a key regulator of immunological reactivities. When engaged together with the T cell antigen receptor, CD4 enhances immune reactions, whereas when ligated independently of the antigen receptor CD4 inhibits the activation of T cells or initiates their deletion. CD4 serves also as a receptor for the human immunodeficiency virus (HIV), which binds the receptor with high avidity through its envelope molecule, gp120. Studies in tissue culture have shown that its affinity to CD4 gives the virus opportunities to utilize CD4‐mediated signaling and to manipulate immunocytes. We show here in human CD4 transgenic mice that appropriately cross‐linked HIV envelope protein causes massive deletion of HIV‐reactive T cells in vivo.
Fate of allogeneic or syngeneic cells in intravenous or portal vein injection: Possible explanation for the mechanism of tolerance induction by portal vein injection
Authors: Zhang Yongfa , Yasumizu Ryoji , Sugiura Kikuya , Hashimoto Futoshi , Amoh Yasuo , Lian Zhexiong , Cherry  , Nishio Nohuhiro , Ikehara Susumu 
Published: March 2007

AbstractIn this report we examine the fate of donor cells injected via different routes. When PKH‐26‐labeled C57BL/6 (B6) spleen cells were intravenously (i.v.) injected into BALB/c mice, the donor cells were rejected within 3 days. In contrast, when the same B6 spleen cells were portal venously (p.v.) injected, they were trapped in the recipient liver. When allogeneic or syngeneic whole bone marrow cells (BMC) or cells in a hemopoietic stem cell (HSC)‐enriched fraction were either i.v. or p.v. injected, the cells accumulated in the liver. The cells trapped in the liver were found to be wheat germ agglutinin (WGA)‐positive HSC. When B6 thymocytes were p.v. or i.v. injected into BALB/c mice, they were rapidly rejected. When BALB/c mice were i.v. preimmunized with unlabeled B6 spleen cells, BMC or thymocytes, the p.v. or i.v. injected PKH‐26‐labeled B6 spleen cells were rejected rapidly (within 2 days). In contrast, when BALB/c mice were p.v. preimmunized with B6 spleen cells or BMC, the p.v. or i.v. injected PKH‐26‐labeled B6 spleen cells were not rejected. The cells responsible for the tolerance induction were found to be HSC trapped in the liver. Delayed‐type hypersensitivity assays revealed that the tolerance could be maintained for more than 49 days by p.v. injection plus i.v. injection (at intervals of 2 weeks) of HSC. These findings indicate that HSC trapped in the liver play a crucial role in the induction and maintenance of p.v. tolerance.
The degree of CD8 dependence of cytolytic T cell precursors is determined by the nature of the T cell receptor (TCR) and influences negative selection in TCR‐transgenic mice
Authors: Auphan Nathalie , Curnow John , Guimezanes Annick , Langlet Claire , Malissen Bernard , Mellor Andrew , Schmitt‐Verhulst Anne‐Marie 
Published: March 2007

AbstractAlthough much has been learned about CD8 structure‐function properties, it has so far not been tested whether the nature of the TCR is sufficient to transfer the property of CD8 dependence versus non‐dependence to CD8+ cytotoxic T lymphocytes (CTL) and their precursors differentiating in T cell receptor (TCR)‐transgenic (Tg) mice. In the present study, we compared the characteristics of dependence on CD8 for stimulation of CTL precursors and antigen‐specific cytolysis by CD8+ T cells from two TCR‐Tg mice expressing respectively the TCR (Tg) from a “CD8‐dependent” and from a “CD8‐independent” CTL clone, which were both reactive against the H‐2Kb alloantigen and originated from H‐2k mice. The results indicate that the property of the Tg+CD8+ cells from H‐2k TCR‐Tg mice corresponds to that of the CTL clone of origin, demonstrating that it is linked to the nature of the TCR. Consistent with this property, Tg+CD4+ cells could also differentiate into H‐2Kb‐specific CTL when originating from the “CD8‐independent”, but not from the “CD8‐dependent” Tg‐TCR. The influence of the property of “CD8 dependence” on negative selection occurring in TCR‐Tg H‐2klb mice was apparent at two levels: (i) in the thymus, the extent of deletion was much more pronounced for the “CD8‐independent” TCR‐Tg mice; (ii) in the periphery, Tg+(hi) cells with low to negative CD8 expression were present for the “CD8‐dependent” Tg‐TCR, whereas only Tg+CD4−CD8− cells with low surface Tg‐TCR and CD3 expression were found for the “CD8‐independent” Tg‐TCR, indicating that Tg+CD4−CD8− cells are susceptible to tolerance induction involving TCR/CD3 surface down‐modulation. Furthermore, different in vitro conditions led to H‐2Kb‐induced stimulation of Tg+CD4−CD8− cells to differentiate into CTL detected in an anti‐TCR clonotypic monoclonal antibody redirected cytolysis assay. Culture in interleukin‐2 of H‐2klb Tg+CD4−CD8− cells was sufficient to induce CTL activity in the “CD8‐independent” model, whereas stimulation with cells which overexpressed H‐2Kb was required in addition to interleukin‐2 to induce CTL differentiation in the “CD8‐dependent” model. These data suggest that peripheral Tg+CD4−CD8− cells present in a situation of in vivo tolerance to H‐2Kb can still be triggered by H‐2Kb with a sensitivity correlated with the degree of CD8 dependence.
Multiple self epitopes on the Rhesus polypeptides stimulate immunologically ignorant human T cells in vitro
Authors: Barker Robert N. , Elson Christopher J. 
Published: March 2007

AbstractThe extent of autoreactive T cell repertoire in the normal individual has previously been unclear. Here we demonstrate that T cells from healthy humans can be stimulated by multiple epitopes on a self protein to give primary proliferative responses in vitro. Synthetic 15‐mer peptides, corresponding to the sequence of a human red blood cell Rhesus polypeptide, were tested for the ability to stimulate normal T cells. Multiple peptides were found to provoke responses reproducibly, and the proliferation could be blocked consistently by antibodies to HLA‐DR, but not ‐DP or ‐DQ. T cells from each donor proliferated in response to different patterns of peptides, but this variation in pattern was less marked in individuals with the same HLA‐DR type. The responses were comparable in kinetics to those elicited by the non‐recall foreign antigen keyhole limpet hemocyanin, and the responding cells are most commonly derived from the CD45RA+ subpopulation, indicating that they had not been activated in vivo. It is considered that T cells are “immunologically ignorant” of many self peptides, presumably because they correspond to cryptic epitopes that are not normally presented in vivo.
Expression and function of CD59 on colonic adenocarcinoma cells
Authors: Bjøge Line , Vedeler Christian A. , Ulvestad Elling , Matre Roald 
Published: March 2007

AbstractThe expression and function of CD59, a 19–25 kDa membrane glycoprotein that inhibits formation of the membrane attack complex of complement, was analyzed on normal and malignant human colonic epithelial cells. Analysis by immuno‐fluorescence demonstrated a weak apical expression of CD59 on normal intestinal epithelium, with an increased expression on adenocarcinoma cells. The expression of CD59 was greatest on tumor cells with poor differentiation. The functional activity of CD59 on human adenocarcinoma cells was investigated using the colonic adenocarcinoma cell line HT29, CD59 on HT29 cells was glycosyl‐phosphatidylinositol‐linked, and had a molecular mass of 19–25 kDa. HT29 cells expressed approximately four times more CD59 than leukocytes, and showed a high resistance to antibody‐dependent complement‐mediated lysis. Blocking of CD59 with divalent antigen‐binding F(ab′)2 fragments of the anti‐CD59 monoclonal antibody 1F5 resulted in a dose‐dependent increase in complement‐mediated lysis, suggesting that CD59 may be of importance in protecting colonic adenocarcinoma cells against complement‐mediated cytolysis.
Flexibility of the T cell receptor repertoire
Authors: Liang Hong‐Erh , Chen Ching‐Chen , Chou Ding‐Li , Lai Ming‐Zong 
Published: March 2007

AbstractAlternative T cell receptor (TcR) gene usage between mice of different Mls alleles has been demonstrated in a number of T cell responses. A clear illustration of a flexible TcR Vβ usage in the same strain of mice remains to be established. Using a model system in which I‐Ek‐restricted T cells recognizing λ repressor cI protein (cI) 12–26 and pigeon cytochrome c (pcc) 81–104 predominantly use Vβ3 in B10.A and B10.BR mice, and Vβ1 in Mls‐2a‐bearing A/J and C3H mice, we have first demonstrated that the hierarchy of TcR Vβ usage can not be inferred from one strain of mice to the other. The presumed flexibility of Vβ3 to Vβ1 did not exist in B10.BR mice in the given responses. Instead, a switch of dominant TcR from Vβ1/Vβ3 to Vβ8 was identified in C3H and B10.BR mice. In contrast, there was an absolute rigidity in TcR repertoire usage in some mouse strains such as A/J. The lack of flexibility was not due to slow generating kinetics of replacing T cells, since A/J mice treated with staphylococcal enterotoxin A from birth on still responded poorly to cI 12–26 and pcc 81–104. Therefore, whether TcR Vβ usage in a T cell response would be flexible or rigid is highly dependent on each strain of mice. However, even the plasticity seen in B10.BR mice is very limited and further tolerance of the Vβ8+ population results in non‐responsiveness toward the given antigens.
A Vβ.2‐specific superantigen from exogenous mouse mammary tumor virus carried by FM mice
Authors: Yoshimoto Takayuki , Nagase Hisashi , Nakano Hideki , Matsuzawa Akio , Nariuchi Hideo 
Published: March 2007

AbstractA number of endogenous mouse mammary tumor virus (MMTV) proviruses encode superantigen that have the ability to stimulate T cells with a certain T cell receptor (TCR) β‐chain variable region (Vβ) and to mediate the Vβ‐specific clonal deletion. The tumorigenic milk‐borne MMTV carried by C3H and GR mice also have superantigenic properties in vivo. In the present study we identified and characterized a novel Vβ8.2‐specific superantigen of exogenous MMTV carried by FM mice. The open reading frame (ORF) in the 3′ long terminal repeat of the MMTV was cloned by polymerase chain reaction with primers corresponding to conserved regions spanning the ORF coding region. Sequence analysis of the ORF revealed that there is no sequence identical to those in other known MMTV in the carboxy terminus implicated in TCR Vβ recognition. Subcutaneous injection of the virus into adult BALB/c mice induced an approximately three‐ to fourfold enlargement of draining lymph nodes and a substantial increase of Vβ8.2+ CD4+ T cells in the lymph nodes within 6 days. The exposure of newborn BALB/c mice to the virus by foster nursing resulted in a marked deletion of Vβ8.2+ cells both in CD4+ and CD8+ T cells. Thus, a novel milk‐borne MMTV in FM mice expresses strong superantigenic properties capable of stimulating Vβ8.2+ T cells. Vβ8.2+ T cells have been demonstrated to be frequently involved in recognition of conventional antigens and responsible for autoimmune diseases such as experimental allergic encephalomyelitis. Therefore, the MMTV (FM) may provide a new mouse model system for inducing immunodeficiency or autoimmune disease by retroviral infection.
The invariant chain inhibits presentation of endogenous antigens by a human fibroblast cell line
Authors: Dodi Anthony I. , Brett Sarah , Nordeng Tommy , Sidhu Sasvinder , Batchelor Richard J. , Lombardi Giovanna , Bakke Oddmund , Lechler Robert I. 
Published: March 2007

AbstractThe human fibroblast cell line, M1, expressing the products of transfected DRA and DRB1*0101 genes (M1‐DR1) was unable to present intact influenza antigens to a series of DR1‐restricted human T cell lines and clones, but was fully able to present synthetic peptides for T cell recognition. In contrast, M1‐DR1 cells infected with live influenza virus were recognized by two polyclonal hemagglutinin‐ or whole virus‐specific T cell lines and one of four T cell clones. This difference could not be accounted for simply by the ability of infectious virus to overcome a defect in antigen uptake by the M1‐DR1 cells, in that direct studies of endocytosis showed that the M1 cells were more efficient than human B cells in the internalization of exogenous protein. These data suggested that the M1 cells were unable to present exogenous antigens but were capable of loading major histocompatibility complex (MHC) class II molecules with peptides derived from endogenous antigens. To investigate this further, the M1‐DR1 cells were super‐transfected with a cDNA encoding the p33 and p35 forms of the human invariant chain (Ii). Expression of the Ii chain was detected by intracytoplasmic staining of transfectants, and by metabolic labeling. Equimolar amounts of the p33 and p35 forms were detected, and the high level of p35 Ii was reflected by extensive retention of Ii protein in the endoplasmic reticulum. Addition of the Ii chain led to no recovery of presentation of intact antigens with DR1, but inhibited the presentation of live virus. These data indicate that MHC class II molecules in the M1‐DR1 cells can be loaded with peptides derived from endogenous proteins, possibly in the biosynthetic pathway, and that the Ii chain has a role in limiting this route of class II antigen presentation.
A novel anti‐rat CD18 monoclonal antibody triggers lymphocyte homotypic aggregation and granulocyte adhesion to plastic: Different intracellular signaling pathways in resting versus activated thymocytes
Authors: Pavlovi Miloš D. , Čolić Miodrag , Pejnović Nada , Tamatani Takuya , Miyasaka Masayuki , Dujić Aleksandar 
Published: March 2007

AbstractWe have raised a monoclonal antibody (mAb), NG2B12, directed against rat CD18, capable of inducing lymphocyte homotypic adhesion and granulocyte adherence to plastic. NG2B12‐induced aggregation is temperature sensitive and requires metabolic energy, an intact cytoskeleton and the presence of Mg2+, but is independent of protein synthesis. Ca2+ is not only dispensable but exerts a suppressive effect on the NG2B12‐induced adhesion. The adhesion is readily observed in thymocytes and concanavalin A blasts of thymocytes and splenocytes but is very weak in resting spleen and lymph node cells. NG2B12 also enhances phorbol 12‐myristate 13‐acetate (PMA)‐induced aggregation in an additive fashion. The NG2B12‐induced homotypic adhesion is mediated by LFA‐1. mAb against ICAM‐1 completely inhibited the induced adhesion of activated cells but inhibited only partially and in a time‐dependent manner the adhesion of resting thymocytes. The activation of protein phosphatases 1 and 2A (as assessed by the use of okadaic acid) is necessary for the NG2B12‐induced adhesion of both resting and activated thymocytes. In contrast, H‐7 (an inhibitor of protein kinase C and A), substantially suppressed the adhesion of resting thymocytes, whereas W‐7 (an inhibitor of calmodulin‐dependent protein kinase) inhibited the adhesion of activated thymocytes. NG2B12 induces both adherence to plastic and homotypic aggregation of granulocytes; the events being blocked by anti‐CD18 (WT.3) and anti‐CD11b/CD11c (OX‐42) mAb, augmented by okadaic acid and not modified by H‐7 and W‐7. Additionally, we have demonstrated that NG2B12 and PMA employ distinct intracellular signaling pathways in inducing adhesion of both thymocytes and granulocytes.
A λ1 transgene under the control of a heavy chain promoter and enhancer does not undergo somatic hypermutation
Authors: Hengstschläger Markus , Williams Marna , Maizels Nancy 
Published: March 2007

AbstractTo identify cis‐acting elements responsible for targeting somatic hypermutation to immunoglobulin variable regions, we generated transgenic mice which carry a rearranged λ1 gene regulated by the heavy chain intron enhancer, Eμ, and the heavy chain promoter PH186.2 from the VH186.2 variable region. C57BL/6 × SJL founders were bred with C57BL/6 mice to establish a line carrying a single copy of the transgene. Somatic hypermutation was studied by generating hybridoma cell lines from mice immunized with the hapten (4‐hydroxy‐3‐nitrophenyl)acetyl (NP) coupled to chicken gamma globulin. The immune response in this transgenic line was dominated by the endogenous VH186.2 heavy chain variable region and the transgenic λ1 light chain, and the transgene was actively expressed in all hybridomas analyzed. In this work we show that the transgenic Vλ1 regions do not undergo hypermutation, despite high levels of expression, while the expressed heavy chain V regions accumulate mutations at a rate typical of the NP response in C57BL/6 mice. Thus, within the same B cell, the PH186.2 promoter in connection with Eμ drives efficient expression of both a VH and a Vλ region, but only the VH is a target for somatic hypermutation. Our observations show that cis‐acting sequences that activate immunoglobulin gene transcription are not sufficient to target somatic hypermutation.
Entry of B lymphocytes into the persistent cell pool in non‐immunized mice is not accompanied by somatic mutation of VH genes
Authors: Chies José A. B. , Lembezat M. P. , Freitas A. A. 
Published: March 2007

AbstractIn this study we compare VH‐gene repertoires of short‐lived and persistent B lymphocytes in normal nonimmunized mice. Enriched populations of persistent peripheral B cells were obtained in vivo either by (i) repeated injections with hydroxyurea or (ii) maintained ganciclovir administration to herpes simplex virus‐1 thymidine kinase transgenic mice. Both approaches have previously been shown to deplete newly formed, short‐lived B cells. VH genes expressed by persistent or unselected B cell populations were amplified by polymerase chain reaction, cloned using the λ‐ImmunoZAP system (Stratagene) and sequenced. The results presented here concern a total of 116 complete VH sequences from two VH gene families of established germ‐line composition: VH7183 and VHX24. No differences were found between the two cell populations as to usage of D or JH segments and to the presence of N sequence additions at D/JH or VH/DJH junctions and CDR3 length. Over 90% of the sequenced VH genes were of germ‐line arrangement with no evidence of somatic mutation. These results show that persistent B cells in normal mice are not of embryonic origin and that somatic hypermutation is not necessary for B cell survival. They also suggest that a significant fraction of persistent IgM+ B cells in normal mice are not generated by conventional antigenic stimulation and could represent a novel class of “memory” cells expressing germ‐line repertoires.
Lipopolysaccharide‐dependent transactivation of the temporally regulated immunoglobulin heavy chain 3′ enhancer
Authors: Arulampalam Velmurugesan , Grant Patrick A. , Samuelsson Annika , Lendahl Urban , Pettersson Sven 
Published: March 2007

AbstractTo execute different biological functions, the expression pattern of immunoglobulin heavy chain genes (IgH) is altered during B lymphocyte differentiation. Early in B cell differentiation, it is assumed that the heavy chain promoter and the intragenic enhancer (Eμ) ensure VDJ recombination. This leads to the expression of the immunoglobulin receptor on the cell surface. An additional strong enhancer in the far 3′ end of the IgH locus has, however, prompted a re‐evaluation of the regulation of immunoglobulin gene expression. To define the temporal and spatial regulation of the IgH 3′ enhancer, transgenic mice harboring an enhancerdependent reporter gene construct were generated. Here we demonstrate that IgH 3′ enhancer activity is largely restricted to activated immunocompetent B cells. Furthermore, the enhancer can be transactivated following mitogen stimulation with lipopolysaccharide and 12‐O‐tetradecanylphorbol 13‐acetate. We propose a model whereby 3′ enhancer activation is linked to the activation of resting immunocompetant B cells. The implications of the enhancer being active in late B lymphocyte differentiation, when heavy chain class switching occurs, are discussed.
Lymphocyte populations and immune responses in CD5‐deficient mice
Authors: Tarakhovsky Alexander , Müller Werner , Rajewsky Klaus 
Published: March 2007

AbstractThe CD5 antigen is expressed at a high level on T cells from early on in thymocyte ontogeny and continues to be expressed on the surface of all mature T cells. In addition, it marks a population of B lymphocytes (B‐1a) with distinct physiological properties. To study the in vivo function of CD5, the murine gene was inactivated using the technique of homologous recombination in embryonic stem cells. In homozygous mutant mice the CD5 antigen is not expressed on the surface of either T or B lineage cells, indicating that in both cell populations this antigen is encoded by the same gene. CD5‐deficient (CD5T) mice are healthy and populations of T and B lymphocytes in these mice look unchanged when compared to control mice. The mutant mice are able to mount effective immune responses to T cell‐dependent and ‐independent antigens.
Expression of a transgenic class II Ab gene confers susceptibility to collagen‐induced arthritis
Authors: Brunsberg Ulrica , Gustafsson Kenth , Jansson Liselotte , Michaëlsson Erik , Ährlund‐Richter Lars , Pettersson Sven , Mattsson Ragnar , Holmdahl Rikard 
Published: March 2007

AbstractThe major histocompatibility complex (MHC) class II region is assumed to influence autoimmune diseases such as rheumatoid arthritis. In the mouse, the H‐2q haplotype is associated with susceptibility to collagen‐induced arthritis, while the H‐2p haplotype is not. The class II A molecules of these haplotypes differ by only four amino acids in the first domain of the β chain. To test if this difference accounts for the MHC influence on susceptibility to collagen‐induced arthritis, H‐2p mice were made transgenic with an Abp gene altered to resemble the Abq gene. The transgenic Aβ chain hybridized with the Aαp chain and was shown to be physiologically expressed by testing antigen‐presentation capacity to Aq‐restricted T cell hybridomas and with FACS analyses. These transgenic mice developed an autoimmune response to type II collagen and also collagen‐induced arthritis. The data unequivocally suggest the Ab gene as a major genetic susceptibility locus for autoimmune collagen‐induced arthritis.