bluuebunny/crossref_metadata_2025_split huggingface dataset:
An explanation for the defect in secretion of IgM Mott cells and their predominant occurrence in the Ly‐1 B cell compartment
Authors: Tarlinton David , Förster Irmgard , Rajewsky Klaus 
Published: March 2007

AbstractMott cells are a variant form of plasma cell in which the immunoglobulin (Ig), rather than being secreted, accumulates in rough endoplasmic reticulum‐derived vesicles called Russell bodies. We have examined the molecular cause of this defect and the in vivo origin of IgM Mott cells. Our examination of the Ig variable region gene sequences of two IgM Mott hybridomas derived from C. B‐20 Ly‐1 B cells showed all to be germ line. In a series of mix and match transfection experiments, the Mott phenotype was only reconstituted when the original Mott specificity was expressed as an IgM, suggesting that both the specificity and the isotype were critical to the formation of Russell bodies.Based on our finding that Russell body formation was dependent on the Ig isotype being IgM, we suggest that the Mott phenotype is apparent only after differentiation of B cells into plasma cells and that probably the major cause of the IgM Mott phenotype is low‐affinity interaction of the Mott Ig with some as yet unknown intracellular component(s) being stabilized by the intrinsic high avidity of the pentameric secreted form of IgM. Consistent with this proposal was the finding that after in vitro lipopolysaccharide (LPS) stimulation of sorted Ly‐1 B cells derived from C.B‐20 mice, Mott cells represented up to 5% of the IgM plasma cells in the culture. LPS stimulation of conventional B cells also induced the appearance of IgM Mott cells, but at the much reduced level of 0.1%, suggesting that the major, if not the only, source of Mott cells in vivo is the Ly‐1 B cell population. A possible causal relationship between the elevated frequency of Mott cells in the Ly‐1 B cell‐derived LPS blasts and the repertoire selection inherent in the development of these B cells is discussed.
CD45 modulates T cell receptor/CD3‐induced activation of human thymocytes via regulation of tyrosine phosphorylation
Authors: Turka Laurence A. , Kanner Steven B. , Schieven Gary L. , Thompson Craig B. , Ledbetter Jeffrey A. 
Published: March 2007

AbstractStimulation of thymocytes or mature T cells via the T cell receptor (TcR)/CD3 complex activates a cascade of processes inducing cells to enter the cell cycle. A key step is the activation of phosphatidylinositol‐specific phospholipase C (PI‐PLC) within seconds following TcR/CD3 stimulation, an event which is strongly enhanced by co‐ligation of the CD4 (or CD8) accessory molecule with TcR/CD3. In contrast, co‐ligation of CD45 inhibits the same TcR/CD3 responses. The machinery which couples the TcR/CD3 complex, CD4, and CD45 to PI‐PLC appears to involve regulation of tyrosine phosphorylation, as the TcR/CD3 and CD4 receptors are associated with the tyrosine kinases p59fyn and p56lck, respectively, and CD45 has intrinsic tyrosine phosphatase activity. Here, we have examined the ability of CD45 to regulate signal transduction via TcR/CD3 in human thymocytes. Co‐cross‐linking CD45 to the TcR/CD3 complex strongly suppressed the tyrosine phosphorylation of several intracellular substrates normally seen following TcR/CD3 stimulation. This effect of CD45 was associated with inhibition of a rise in intracellular calcium following TcR/CD3 ligation. Since TcR/CD3 stimulation of mature T cells induces tyrosine phosphorylation of PLCγ1, we investigated this phenomenon in thymocytes, and asked whether ligation of CD45 might regulate this process. By immunoprecipitation we found that TcR/CD3 stimulation induced tyrosine phosphorylation of PLCγ1, an effect which was enhanced by co‐cross‐linking CD4 to TcR/CD3. In contrast, co‐ligation of CD45 strongly blocked PLCγ1 phosphorylation induced by either stimulus. Consistent with previous findings in mature T cells, CD45 cross‐linking was able to partially inhibit TcR/CD3‐induced thymocyte proliferation when interleukin 2 was used as a second signal, but almost completely (80%–90%) blocked proliferation when anti‐CD28 mAb was used as the second signal, suggesting that CD45 cross‐linking may be able to block interleukin 2 production via the CD28 pathway. These effects of CD45 on TcR/CD3 signaling and proliferation in thymocytes point towards a potential role for this pathway in thymic selection.
T cell receptor diversity and activation markers in the Vδ1 subset of rheumatoid synovial fluid and peripheral blood T lymphocytes
Authors: Bucht Anders , Söderström Kalle , Hultman Thomas , Uhlén Mathias , Nilsson Ethel , Kiessling Rolf , Grönberg Alvar 
Published: March 2007

AbstractIn the present study we have characterized the γ/δ T cell receptor (TcR) population in synovial fluid (SF) and peripheral blood (PB) of patients with chronic inflammatory arthritis. By double staining we have shown that (a) synovial Vδ1+ cells have a high expression of activation markers CD45R0 (“memory cells”) and HLA‐DR as compared to PB, indicating a preactivated population of Vδ1‐carrying T cells in vivo and (b) interleukin 2‐induced expansion of synovial cells yields a high proportion of γ/δ in most samples expressing predominantly the Vδ1 TcR. Junctional sequence analysis of the TcR δ chain from interleukin 2‐expanded PB cell lines demonstrated a polyclonal Vδ1 population in three out of three samples. In SF cell lines three out of four samples were polyclonally expanded. In SF from one patient, however, a limited repertoire of expressed Vδ1 genes was found. Altogether, our data demonstrate the presence of preactivated Vδ1‐expressing cells in the synovial compartment. This Vδ1 population is predominantly polyclonal, except in one patient where oligoclonally expanded Vδ1 cells were detected.
Differential sensitivity of freshly isolated and cultured murine Langerhans cells to ultraviolet B radiation and chemical fixation
Authors: Tang Aimin , Udey Mark C. 
Published: March 2007

AbstractPrevious studies have demonstrated that low doses of ultraviolet B (UVB) radiation (100 J/m2) abrogate the accessory function of freshly isolated murine epidermal Langerhans cells (fLC) and cause a parallel decrease in the ability of LC to express increased amounts of ICAM‐1 (CD54) in vitro. We have subsequently observed that the accessory cell function of cultured LC (cLC), as assessed by their ability to support anti‐CD3 monoclonal antibody (mAb)‐induced T cell mitogenesis, was not inhibited by levels of UVB exposure (100 J/m2) that completely inhibited the function of fLC, although exposure of cLC to UVB radiation (100 J/m2) resulted in a decrease in the level of ICAM‐1 expression on most cLC and a concomitant decrease in cLC survival during a subsequent 24‐h incubation. Time course studies revealed that T cells stimulated with anti‐CD3 mAb in the presence of cLC became committed to proliferate 4‐8 h after culture initiation, while 24–30 h of co‐culture was required for irreversible T cell activation when fLC were utilized as accessory cells. In addition, paraformaldehyde (PFA)‐fixed (non‐viable) cLC supported anti‐CD3 mAb‐induced T cell proliferation, whereas PFA‐fixed fLC were ineffective. We propose that cLC are functionally resistant to low doses of UVB radiation and chemical fixation because cLC express sufficient levels of the adhesion or co‐stimulatory molecules [including ICAM‐1 and Mac‐1 (CD11b/CD18)] required to induce T cell activation. Conversely, fLC are sensitive to the effects of UVB radiation and chemical fixation because these physicochemical agents prevent acquisition of critically important surface molecules in culture.
Mapping of the human VLA‐α4 gene to chromosome 2q31‐q32
Authors: Fernández‐Ruiz Elena , de Villena Fernando Pardo‐Manuel , Rubio Miguel Angel , Corbi Angel L. , De Córdoba Santiago Rodriguez , Sánchez‐Madrid Francisco 
Published: March 2007

AbstractThe integrin VLA‐4 (α4: β1; CD49d/CD29) is involved in both cellular adhesion to extracellular matrix and cell‐cell interactions. We have determined that the human gene coding for VLA‐α4 is located on the long arm of chromosome 2 by using fluorescence in situ hybridization. The VLA‐α4 gene has been more precisely mapped to the 2q31‐q32 region after GTG banding (G‐bands by trypsin using Giemsa). These data suggest that the VLA‐4 gene belongs to the COL3A1‐(ELN‐FN)‐COL6A3 linkage group and establishes a potential genetic relationship between the α4 and αv integrin subunits.
Characterization of rat encephalitogenic T cells bearing non‐Vβ8 T cell recepotors
Authors: Sun Deming , Gold Daniel P. , Smith Lawrence , Brostoff Steven , Coleclough Christopher 
Published: March 2007

AbstractIn this study, we demonstrate that T cell lines specific for a synthetic peptide representing sequence 87 to 99 of myelin basic protein (MBP) are encephalitogenicin Lewis rats. However, unlike syngeneic T cells specific for MBP residues 68 to 88 which exclusively use Vβ8 in their antigen receptors, these cells do not. None of the 10 T cell lines and T hybridomas specific for MBP (87–99) used Vβ8 in their T cell receptors. Our results document for the first time that rat encephalitogenic T cells do not exclusively use Vβ8 in T cell receptors that rat encephalitogenic T cells specific for MBP (87–99) are heterogeneous and that MBP (87–99) contains at least two epitopes for rat T cells.
Extrathymic origin of Vγ1/Vδ6 T cells in the skin
Authors: Ota Yasuo , Kobata Tetsuji , Seki Makiko , Yagita Hideo , Shimada Shinji , Huang Ying‐Ying , Takagaki Yohtaroh , Okumura Ko 
Published: March 2007

AbstractThe dendritic epidermal cells (dEC) from young (8‐week‐old) athymic mice were found to express mRNA for γ/δ T cell receptors (TcR). The mRNA found in the dEC from athymic mice was expressed only for Vγ1‐Jγ4‐Cγ4 and Vδ6‐Jδ‐Cδ with both chains having productive rearrangements and junctional diversity. On the other hand, the dEC from euthymic mice carried Vγ5‐Jγ1‐Cγ1 and Vδ1‐Jδ2‐Cδ in addition to the Vγ1/Vδ6 subset found in athymic mice. Therefore, this Vγ1/Vδ6 subset, which has been implicated in the murine γ/δ T cell responses to mycobacterial antigens and self heat‐shock proteins, is the product of extrathymic maturation in the dEC from both athymic and euthymic mice.
Interleukin 6‐induced differentiation of a human B cell line into IgM‐secreting plasma cells is mediated by c‐fos
Authors: Körholz Dieter , Gerdau Stefan , Enczmann Jürgen , Zessack Norbert , Burdach Stefan 
Published: March 2007

AbstractThe role of the protooncogene c‐fos in interleukin (IL) 6‐induced B cell differentiation was assessed. Treatment of SKW 6.4 cells with IL 6 induced a transient and early stimulation of c‐fos sense mRNA expression. The effect appeared within 30 min and returned to basal levels after 2 h. The addition of antisense oligonucleotides to c‐fos significantly inhibited IL 6‐induced IgM production by SKW 6.4 cells (p < 0.001), whereas control oligonucleotides had no inhibitory effect. These results indicate that activation of c‐fos is involved in IL 6‐induced differentiation of SKW 6.4 cells into IgM‐secreting cells.
Gene transfer experiments imply instructive role of major histocompatibility complex class I molecules in cellular peptide processing
Authors: Wallny Hans‐Joachim , Rötzschke Olaf , Falk Kirsten , Hämmerling Günther , Rammensee Hans‐Georg 
Published: March 2007

AbstractDBA/2‐derived mouse tumor cells were transfected with the H‐2Kb gene. Naturally processed minor histocompatibility (H) peptides were extracted from both transfected and non‐transfected cells by acid elution, and were separated by high‐performance liquid chromatography. Kb‐restricted minor H epitopes corresponding to H‐4b and mapki, both encoded by non‐major histocompatibility complex genes of DBA/2, were readily detected by the respective cytotoxic T lymphocyte in peptides extracted from Kb‐transfected, but not from non‐transfected or Db‐transfected cells. Titration experiments indicated at least 3000‐fold less copies of correctly processed Kb‐restricted epitopes in cells without Kb as compared to cells with Kb. Since we estimate the copy number of Kb‐restricted H‐4b epitopes in Kb‐expressing transfectants to be less than 1000 per cell, the pool size of H‐4b epitopes correctly processed in the absence of Kb should be less than 1/3 copy per cell.
High frequency of malaria‐specific T cells in non‐exposed humans
Authors: Zevering Yinka , Amante Fiona , Smillie Anne , Currier Jeff , Smith Gale , Houghten Richard A. , Good Michael F. 
Published: March 2007

AbstractA major goal of current candidate malaria vaccines is to stimulate the expansion of clones of malaria‐specific lymphocytes. We have examined the in vitro T cell responses of a group of malaria exposed and non‐exposed adult Caucasian donors to recombinant circumsporozoite (CS) proteins, one of which is undergoing clinical trials, to blood‐stage parasites, and to synthetic peptides copying the CS protein and defined blood‐stage proteins. In nearly all individuals tested, CD4 T cell proliferation or lymphokine production occurred in response to whole parasite or CS protein stimulation, and T cells from many individuals responded to synthetic peptides. T cell responses were major histocompatibility complex‐restricted, and stimulation of T cells with malaria parasites or CS protein did not appear to expand a population of T cell receptor γ/δ cells. Malaria‐specific responses were independent of prior malaria exposure, and in some cases exceeded the magnitude of response to tetanus toxoid. Specific T cells are present in high frequency in the peripheral blood of many donors who have never been exposed to malaria. Although malaria‐specific CD4 T cells play an important role in immunity, these data question whether vaccines need to stimulate such cells, and focus attention on other aspects of malaria immunity which may be more critical to a successful vaccine.
Complement‐mediated follicular localization of T‐independent type‐2 antigens: the role of marginal zone macrophages revisited
Authors: van den Eertwegh Alfons J. M. , Laman Jon D. , Schellekens Marc M. , Boersma Wim J. A. , Claassen Eric 
Published: March 2007

AbstractIn this study we demonstrate a hitherto undescribed phenomenon, namely that thymus‐independent type‐2 antigens (TI‐2 Ag) localize in splenic follicles within 1 h after administration. The follicular localization of 2,4,6‐trinitrophenyl (TNP)‐Ficoll was not antibody mediated. In addition in case of high‐dose administration we observed a relatively large amount of TI‐2 Ag in marginal zone macrophages. However, after low‐dose administration we observed a preferential localization of TNP‐Ficoll in the splenic follicles. Detection of TNP‐haptenated Ag in cryostat sections of murine spleens was performed with a high‐affinity TNP‐specific monoclonal antibody conjugated to β‐galactosidase. Within minutes after injection the TI‐2 Ag localized in the marginal zone, attached to marginal zone macrophages and B cells. Twenty minutes after injection the Ag was also detected in the follicles and gradually accumulated there until 7 h after injection. Thereafter, the amount of follicular Ag gradually decreased but was still detectable up to 14 days after immunization. The follicular localization of TNP‐Ficoll was complement dependent in contrast to the binding to and uptake by marginal zone macrophages. Double staining revealed that Ag was bound by macrophages, B cells and follicular dendritic cells. Haptenated thymus‐dependent (TD) Ag localized exclusively in the red pulp macrophages. In vivo macrophage elimination drastically increased the amount of TNP‐Ficoll in the follicles, and enhanced the humoral immune response at low doses of Ag. Moreover, complement deprivation of mice abrogated the localization of TI‐2 Ag in the follicles, and led to a decreased humoral TI‐2 immune response. In conclusion, we demonstrate for the first time that TI‐2 Ag localize in follicles. Moreover, the presented results provide further evidence that B cells and follicular localized Ag play an important role in the induction of humoral TI‐2 immune responses.
Suppression of interleukin 2 secretion and interleukin 2 receptor expression during tsetse‐transmitted trypanosomiasis in cattle
Authors: Sileghem Maarten , Norman Flynn J. 
Published: March 2007

AbstractInfection with Trypanosoma congolense in cattle was found to be associated with a profound suppression of the host's immune system. Lymph node cells from infected cattle were unable to secrete interleukin 2 (IL 2) in vitro following mitogenic stimulation and the exogenous supply of IL 2 did not restore T cell proliferative responses. This was associated with an impaired expression of the α chain of the IL 2 receptor (IL 2R α). Co‐culture experiments, where cells from an infected animal were mixed with cells from a major histocompatibility complex‐matched normal animal, demonstrated the presence of suppressor cells capable of blocking both IL 2 secretion and IL 2Rα expression. Removal of macrophages by fluorescence‐activated cell sorting abrogated suppression in such co‐cultures. Following depletion of macrophages, lymph node cells from an infected animal expressed IL 2Rα at a normal level, but remained incapable of producing IL 2. Hence, the unresponsiveness was associated with macrophage‐like suppressor cells which operated at the level of both IL 2 secretion and IL 2Rα expression, and to an intrinsic unresponsiveness of the T cells which was restricted to IL 2 secretion.Inhibition of prostaglandin synthesis by addition of indomethacin failed to abrogate suppression of either IL 2 secretion or IL 2Rα expression. This revealed a major difference between the regulation of suppression in murine model infections where the suppression of IL 2 secretion is due to prostaglandin secretion, and the situation in cattle where prostaglandins would not appear to be involved.
Correlation of antibody multireactivity with variable region primary structure among murine anti‐erythrocyte autoantibodies
Authors: Conger John D. , Sage Harvey J. , Corley Ronald B. 
Published: March 2007

AbstractA high proportion of the antibodies in the preimmune repertoire bind to several unrelated antigens and are considered to be multireactive. This property is reportedly associated with the antibodies produced by CD5+ B lymphocytes. Because many antibodies specific for bromelain‐treated mouse red blood cells (BrMRBC) derive from CD5+ B cells, we tested monoclonal antibodies of this specificity for multireactivity. Two variable region combinations, VH11/Vϰ9 and VH12/Vϰ4, account for >80% of this repertoire, but none of these antibodies exhibited a multireactive phenotype. In contrast, three anti‐BrMRBC binding antibodies belonging to the J558 family (BrM1, BrM8, and CH12) showed varying degrees of multireactivity, and bound both highly negatively and positively charged antigens. The amino acid sequences of the VH regions of these antibodies are highly homologous (greater than 85 % identical) and they possess large VH‐D‐J junctions with extensive N‐region insertions. The ϰ chains of two of these antibodies utilize an identical Vϰ gene segment, while the third uses a very different Vϰ with only 50 % homology. The entire H chain V regions of these antibodies are unusually basic, with isoelectric points of 9.5–10, a feature which might be important in promoting interactions with acidic epitopes. The multi‐reactive antibodies also contain regions with a high concentration of hydroxylside chain amino acids, especially in their VH‐D‐J junctions. This region also contains acidic amino acid residues, which may be important in binding of positively charged epitopes. We propose that an open, accessible binding site and a charge polarity may be features which facilitate the binding of charged epitopes, providing a structural basis for multireactivity of at least some antibodies.
Expression of the murine interleukin 6 receptor in hepatoma cells: the intracytoplasmic domain is not required for interleukin 6 signal transduction
Authors: Fiorillo Maria Teresa , Toniatti Carlo , Van Snick Jacques , Ciliberto Gennaro 
Published: March 2007

AbstractThis paper reports on cDNA coding for the 80‐kDa murine IL 6 receptor (mIL 6R) that was cloned from a mouse liver cDNA library. Human hepatoma Hep3B cells transfected transiently or stably with an expression vector carrying the entire coding region for mIL6R become responsive to mouse IL 6 (mIL 6). We monitored response to the cytokine through the transcriptional activation of a co‐transfected IL 6‐inducible human C‐reactive protein (CRP) promoter; response to mIL 6 is lost upon treatment of the cells with increasing amounts of a monoclonal antibody to mIL 6R. mIL 6R mutants have been generated in the carboxy‐terminal portion of the molecule. Their functional analysis in hepatoma cells shows that the intracytoplasmic domain of the receptor is not absolutely essential to IL 6 signal transduction (i.e. CRP promoter activation), but that the last 40 amino acids contribute to maximal IL 6 response in these cells.
Tolerance in the mouse to major histocompatibility complex‐mismatched heart allografts, and to rat heart xenografts, using monoclonal antibodies to CD4 and CD8
Authors: Chen Zonghua , Cobbold Stephen , Metcalfe Su , Waldmann Herman 
Published: March 2007

AbstractMice given a single short course of anti‐CD4 and anti‐CD8 monoclonal antibodies (mAb) became tolerant of major histocompatibility complex (MHC)‐incompatible vascularized heart allografts in a donor‐ and organ‐specific manner. T cell depletion was not important, as blocking antibodies were equally effective. Anti‐CD4 antibody therapy alone was sufficient to establish tolerance. Anti‐CD8 mAb therapy alone was associated with poor recipient survival, although survivors were rendered tolerant. A second donor‐type heart allograft to the neck was always accepted in recipients which had carried the first abdominal heart allograft for over 120 days, with the first heart also continuing to function. However, donor‐type skin grafted at 100 days was sometimes rejected, albeit chronically. Those recipients that accepted the donor‐type skin were able to reject third‐party skin grafts mismatched at the MHC, or over multiple minor differences alone. Thus, the tolerance induced appeared to be donor and tissue specific, although spreading in some cases to tolerance of skin. Similarly donor‐specific tolerance was found when xenogeneic PVG rat hearts were grafted into CBA/Ca mice using the same protocols of anti‐CD4 plus anti‐CD8 mAb. Resolution of the mechanisms underlying these forms of tolerance may permit the design of improved immunosuppressive protocols for human organ transplantation.