bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the autoimmune B cell repertoire in MRL-lpr/lpr mice.
Authors: Klinman D M , Eisenberg R A , Steinberg A D 
Published: December 2022

Abstract
The processes responsible for the production of autoantibodies have been shown to include both Ag-specific and generalized (polyclonal) forms of B cell activation. The relative contribution and temporal association of these processes to the genesis of systemic autoimmunity are incompletely understood. To study this relationship, the B cell repertoires of MRL-lpr/lpr mice were analyzed by ELISA spot assay over an 8-mo period. Between 6 and 12 wk of age, the number of splenic lymphocytes producing antibodies reactive with both autoantigens and conventional Ag increased proportionately. The repertoires of MRL-lpr/lpr mice under 12 wk were dominated by IgM-secreting B cells that showed no bias toward the production of specific autoantibodies. From 12 to 38 wk of age, an increasing proportion of animals developed repertoires dominated by IgG-secreting B cells that were skewed toward reactivity against one or very few (auto)antigens. Although there was no single Ag against which all mice developed skewed reactivity, 55% of MRL-lpr/lpr adults had increased numbers of B cells producing antibodies to the Sm Ag and 13 to 16% developed increased reactivity toward DNA, myosin, histone, thyroglobulin, or T cells. These data indicate that generalized (polyclonal) B cell activation dominates early repertoire development whereas (auto)-antigen-specific responses become increasingly important during the latter stages of disease in these autoimmune-prone mice.
HIV-gp120 can block CD4-class II MHC-mediated adhesion.
Authors: Rosenstein Y , Burakoff S J , Herrmann S H 
Published: December 2022

Abstract
A possible component of the immune dysfunction associated with infection by HIV is the inhibition of CD4 function resulting from the avid binding of soluble HIV envelope glycoprotein (gp120) to cell surface CD4. We assessed CD4 function by measuring the ability of CD4+ T cells to form conjugates with cell size lipid vesicles, artificial target cells (ATC), bearing the natural ligand for CD4, MHC class II proteins. Conjugate formation was a transient process with the greatest number of specific cell to ATC conjugates found after approximately 30 min of incubation at 37 degrees C. Addition of gp120 specifically blocked conjugates between CD4+ cells and class II ATC in a concentration-dependent manner. These data indicate that T lymphocyte adhesion mediated by CD4 is a dynamic event and that binding of gp120 to CD4 is able to disrupt the normal progression of the interaction between CD4+ T lymphocytes and class II+ APC.
IL-2 dependence of the promotion of human B cell differentiation by IL-6 (BSF-2).
Authors: Splawski J B , McAnally L M , Lipsky P E 
Published: December 2022

Abstract
The effect of rIL-6 on the growth and differentiation of highly purified human peripheral blood B cells was examined. IL-6 alone induced minimal incorporation of [3H]thymidine by unstimulated or Staphylococcus aureus (SA)-stimulated B cells and did not augment proliferation induced by SA and IL-2. Similarly, IL-6 alone did not support the generation of Ig-secreting cells (ISC) or induce the secretion of Ig by unstimulated or SA-stimulated B cells. However, IL-6 did augment the generation of ISC and the secretion of all isotypes of Ig induced by SA and IL-2. Maximal enhancement of B cell responsiveness by IL-6 required its presence from the initiation of culture. Delaying the addition of IL-6 to B cells stimulated with SA and IL-2 beyond 24 h diminished its effect on ISC generation. However, increased Ig production but not ISC generation was observed when IL-6 was added to B cells that had been preactivated for 48 h with SA and IL-2. This effect was most marked when the activated B cells were also stimulated with IL-2. IL-6 in combination with other cytokines such as IL-1 and IL-4 did not induce the secretion of Ig or generation of ISC in the absence of IL-2. Moreover, antibody to IL-6 did not inhibit the effect of IL-2 on the growth and differentiation of B cells stimulated with SA, but did inhibit the IL-6-induced augmentation of Ig secretion by B cells stimulated with SA and IL-2. IL-6 alone enhanced T cell dependent induction of B cell differentiation stimulated by PWM. Part of this enhancement was related to its capacity to increase the production of IL-2 in these cultures. These results indicate that IL-6 has several direct enhancing effects on the differentiation of B cells, all of which are at least in part dependent on the presence of IL-2. In addition, IL-6 can indirectly increase B cell differentiation by increasing IL-2 production by T cells.
Generation and use of site-specific antibodies to serum amyloid A for probing amyloid A development.
Authors: Miura K , Ju S T , Cohen A S , Shirahama T 
Published: December 2022

Abstract
Serum amyloid A (SAA) is an acute phase reactant and the putative precursor of an amyloid fibril protein (AA). During amyloidogenesis in mice, the C-terminal portion of SAA that consists of 28 amino acids is cleaved off to produce the 75 amino acid AA. Of three known isotypes of SAA, SAA2 has been identified as amyloidogenic. For differential immunologic recognition of SAA and AA, antisera were generated in rabbits against AA protein and a synthetic peptide corresponding to the C-terminal (amino acids 84 to 103) of murine SAA2. The anti-AA antiserum reacted with AA and SAA, but the anti-peptide antiserum reacted with SAA only. Immunohistochemically anti-peptide antiserum predominantly stained the rims of murine amyloid deposits. In contrast, anti-AA antiserum generated an overall homogeneous staining of amyloid deposits. The data lend support to a view that SAA are concentrated in the vicinity of the surrounding cells (mostly macrophages) where they are processed to AA, or that SAA are deposited initially as components of the amyloid fibrils onto the outside margin of amyloid deposits and the C-terminus is cleaved off as maturation of the amyloid fibril progresses.
Bactericidal/permeability-increasing protein has endotoxin-neutralizing activity.
Authors: Marra M N , Wilde C G , Griffith J E , Snable J L , Scott R W 
Published: December 2022

Abstract
Neutrophil granules contain proteins important in host defense against bacterial pathogens. Granule proteins released from activated neutrophils facilitate opsonization, phagocytosis, tissue digestion, and antimicrobial activity. Three similar, if not identical, neutrophil proteins, bactericidal/permeability-increasing protein (BPI), 57,000 m.w. cationic antimicrobial protein, and bactericidal protein have been described that specifically kill gram negative bacteria. Since LPS is a structure common to all gram-negative bacteria, we investigated whether the microbicidal protein BPI affects biologic activity of LPS in vitro. Human neutrophils can be activated both in vitro and in vivo by LPS. Upon stimulation, surface expression of CR1 and CR3 increases markedly. Using flow microfluorimetry, we analyzed surface expression of CR1 and CR3 as a measure of neutrophil stimulation in response to LPS. CR up-regulation on neutrophils was TNF independent, suggesting direct LPS stimulation of neutrophils in this system. Purified BPI completely inhibited CR up-regulation on neutrophils stimulated with both rough and smooth LPS chemotypes at 1.8 to 3.6 nM (100 to 200 ng/ml). By comparison, the polypeptide antibiotic polymyxin B completely inhibited the same dose of LPS at 0.4 nM. The inhibitory activity of BPI appeared to be specific for LPS because neutrophil stimulation by formylated peptide or TNF was unaffected. The specificity of BPI for LPS was further demonstrated by inhibition of LPS activity in the limulus amebocyte lysate assay. Therefore, the role of BPI in infection may not be limited to its microbicidal activity, but it may also regulate the neutrophil response to LPS.
Short term exposure to cis unsaturated free fatty acids inhibits degranulation of cytotoxic T lymphocytes.
Authors: Richieri G V , Mescher M F , Kleinfeld A M 
Published: December 2022

Abstract
Degranulation of CTL stimulated by alloantigen-bearing target cells is shown to be inhibited by short term exposure to low concentrations of long chain cis unsaturated free fatty acids (FFA), whereas saturated FFA have no effect. The Ag-specific (TCR mediated) stimulation of cloned murine CTL was monitored by changes in intracellular calcium concentrations [( Ca2+]i) using the fluorescence indicator acetoxymethylester of fura-2 and by degranulation as measured by the release of BLT-esterase. Treatment of the CTL cells with any of the physiologically important FFA; oleic (18:1), linoleic (18:2), linolenic (18:3), or arachidonic (20:4) acid, at concentrations between 1 and 10 microM inhibits the target cell-mediated rise in [Ca2+]i which occurs within seconds of stimulation and the release of BLT-esterase, which occurs over a period of 1 to 3 h. These inhibitory effects are observed within seconds to minutes of FFA addition. Inhibition can be reversed by treating cells with fatty acid free BSA and, in agreement with our previous studies, indicates that the effects of FFA are due to physical perturbations of cellular components. To determine the locus of this perturbation, the effect of FFA on the lipid order of CTL plasma membrane was determined using fluorescence polarization of the membrane impermeable probe trimethylammoniumdiphenylhexatriene. Cis unsaturated FFA were found to disorder the lipid acyl chains and the degree of disorder was found to increase with the degree of cis unsaturation. These results, together with the previous studies, suggest that inhibition results from a physical perturbation of plasma membrane lipid order. Moreover, because degranulation requires elevated levels of [Ca2+]i, it is likely that inhibition of degranulation results from a FFA-induced decrease in Ca2+ permeability through the membrane.
Natural antibodies to IFN-gamma in man and their increase during viral infection.
Authors: Caruso A , Bonfanti C , Colombrita D , De Francesco M , De Rango C , Foresti I , Gargiulo F , Gonzales R , Gribaudo G , Landolfo S 
Published: December 2022

Abstract
Natural antibodies to IFN-gamma were found in healthy individuals ranging from newborn babies to adults and, at higher levels, in patients suffering from different viral infections. During a viral infection, the titer of anti-IFN-gamma antibodies was observed to be correlated with the stage of the disease. Antibodies specific to IFN-gamma were affinity purified both from sera taken from healthy individuals and sera from viral-infected patients, by using a rIFN-gamma-coupled CNBr-activated Sepharose 4B column. The antibodies were found to be of the IgG class, and maintained their ability to bind rIFN-gamma. They were then tested for neutralizing activity and none of the IgG preparations we analyzed impaired the antiviral activity of rIFN-gamma. This finding suggests that the antigenic determinants recognized by these antibodies on the IFN-gamma molecule are located outside the site, on the IFN-gamma molecule, responsible for its antiviral activity.
Depletion of CD8+ T cells increases susceptibility and reverses vaccine-induced immunity in mice infected with Trypanosoma cruzi.
Authors: Tarleton R L 
Published: December 2022

Abstract
The role of CD8+ T cells in immune control of Trypanosoma cruzi infection in mice was examined by using in vivo depletion of CD8+ T cells with antibodies. Both the resistant C57BL/6J and the highly susceptible C3H/HeSnJ developed higher parasitemias and increased or earlier mortality when depleted of CD8+ T cells before infection with the Brazil strain of T. cruzi. CD8 depletion also affected the induction and expression of immunity to T. cruzi after vaccination with the avirulent Corpus Christi strain of T. cruzi. C57BL/6J mice depleted of CD8+ T cells either before or after vaccination showed a near total loss of vaccine induced protection. C3H mice were only partially protected by the vaccination procedure but the protection was totally reversed by anti-CD8 treatment. Chronically infected mice that had survived the acute infection were unaffected by CD8 depletion and showed neither a recrudescence of parasitemia nor an increased susceptibility to reinfection. These results suggest that CD8+ T cells play a role in immunity to T. cruzi in the acute phase but possibly not during the chronic phase of infection. Also, immunization with Corpus Christi strain T. cruzi induces an immunity that is distinct from that induced by survival of the acute phase of infection. The mechanism by which CD8+ T cells contribute to control of T. cruzi infection is not known. However, CD8 depletion had no effect on suppressed immune responses, suggesting their function in T. cruzi-infected mice is related more to the cytotoxic activity or cytokine-producing capacity of this subpopulation of T cells.
A membrane-associated form of C-reactive protein is the galactose-specific particle receptor on rat liver macrophages.
Authors: Kempka G , Roos P H , Kolb-Bachofen V 
Published: December 2022

Abstract
Rat liver macrophages express a galactose-specific receptor which mediates endocytosis of particles or neuraminidase-treated blood cells. From rat serum we now have isolated and purified a galactose-specific lectin by affinity chromatography. Comparative analysis of this serum galactose-binding protein with the galactose-particle receptor protein purified from rat liver macrophages and with C-reactive protein (CRP) reveals close relation or identity of these proteins. An apparent m.w. of 30,000 was determined for all three proteins by SDS-PAGE under reducing conditions and m.w. of about 130,000 by native PAGE. All three proteins exhibit the same pentameric, ring-shaped structure in electron microscopy after negative staining. Antibodies raised against the serum galactose-binding protein or against the macrophage receptor cross-react. A mAb specific for rat neo-CRP labels liver macrophages but not hepatocytes and reacts with the isolated protein in a Western blot assay. Furthermore, the galactose-particle receptor can be functionally replaced by purified CRP: the binding capacity for neuraminidase-treated E of receptor-depleted liver macrophages can be restored by preincubation with purified rat CRP. We therefore conclude that CRP occurs as a membrane-associated protein constitutively expressed on liver macrophages functioning as a receptor mediating galactose-specific binding of particulate ligands.
Protection against Leishmania major in BALB/c mice by adoptive transfer of a T cell clone recognizing a low molecular weight antigen released by promastigotes.
Authors: Scott P , Caspar P , Sher A 
Published: December 2022

Abstract
We have shown previously that BALB/c mice can be protected against a fatal infection with Leishmania major by adoptive transfer of a T cell line recognizing a protective soluble fraction (fraction 9) of promastigotes. We now describe the isolation and characterization of a T cell clone (9.1-2) that also transfers protective immunity against Leishmania. After Ag or mitogen stimulation, this clone secrets IL-2 and IFN-gamma, but not IL-4 or IL-5. The clone preferentially recognizes L. major fraction 9, and in addition, soluble Ag from Leishmania donovani, Leishmania amazonensis, and Leishmania braziliensis, but not from the related flagellates, Trypanosoma cruzi or Crithidia fasciculata. Besides being contained in fraction 9, the stimulatory Ag is also released from the parasite, because concentrated promastigote culture supernatants induced IFN-gamma production by 9.1-2. By means of T cell immunoblotting, we determined that 9.1-2 recognized a protein with a relative m.w. between 8,000 and 12,000, and within this region is a predominant protein contained in fraction 9 of approximately 10,000 m.w. These data identify a new candidate Ag for immunization against protozoa belonging to the genus Leishmania.
Antigen recognition by T cells. Quantitative effects of augmentation by antibodies providing accessory interactions.
Authors: Kane K P , Mescher M F 
Published: December 2022

Abstract
Although engagement of the TCR via antibody can be sufficient to trigger T cells, responses to Ag-bearing cells require additional "accessory" interactions in many cases. A method has been developed which allows preparation of surfaces bearing both purified class I alloantigen and coimmobilized antibodies. With this approach, it is possible to mimic such "accessory" interactions and to examine their quantitative effects on triggering via TCR-Ag interaction. Experiments are described which use this approach to examine triggering of degranulation by cloned, allogeneic CTL lines. Coimmobilization of antibodies specific for any of a variety of CTL surface proteins, including CD8, class I MHC proteins, CD45 (T200) and Thy-1, had the effect of decreasing the critical threshold density of Ag necessary to trigger responses, and decreasing by an order of magnitude the density required to stimulate a half-maximal response. Furthermore, in comparison with the 30-min lag seen with Ag alone, response was initiated immediately when an antibody specific for a CTL surface component was present. These results are consistent with the hypothesis that any CTL surface molecule having sufficient affinity for a component of the target surface can contribute to activation via the Ag-specific TCR; and at low Ag density could determine whether any response occurs.
Role of phosphatidylinositol-anchored proteins in T cell activation.
Authors: Presky D H , Low M G , Shevach E M 
Published: December 2022

Abstract
A novel class of cell surface proteins are attached to the plasma membrane via a phosphatidylinositol (PI)-glycan anchoring structure, and these proteins can be selectively removed from the cell surface by the enzyme PI-specific phospholipase C (PI-PLC). Enzyme treatment led to a prolonged reduction in cell surface expression of several PI-anchored proteins. Activation of T cells led to a marked decrease in the ability of PI-PLC to remove PI-anchored surface proteins from the activated T cells. This decrease in PI-PLC sensitivity may reflect an alteration in the PI-glycan anchoring structures, or in a general membrane property, which renders the PI-anchored proteins inaccessible to the enzyme. When murine T lymphocytes were treated with PI-PLC and then stimulated with either Con A, the calcium ionophore A23187 and PMA, or an anti-CD3 mAb, the response to Con A stimulation was inhibited by 90%, whereas the responses to ionophore and PMA or anti-CD3 were not affected. Removal of PI-anchored proteins inhibited an early event in the activation process in response to Con A because both IL-2 production and IL-2R expression were inhibited by the PI-PLC treatment. Inhibition of the Con A response was secondary to removal of a PI-linked protein from the responder T cell population because PI-PLC treatment of T-depleted spleen cells did not alter their ability to act as a source of accessory cells. It is unlikely that removal of the known PI-linked proteins on murine T cells, Thy-1 and Ly-6, can fully account for the inhibition of Con A response because the cell line M2B3, that lacks these surface proteins, responded normally to Con A stimulation. These studies demonstrate that one or more PI-anchored T cell proteins play an important role in an early step of Con A activation, perhaps involving T cell-accessory cell interactions. In contrast, the ability to stimulate T cells by direct cross-linking of TCR/CD3 complex is not dependent on the presence of these PI-anchored proteins.
Antigen-specific sIalo B cells do not secrete IgG2a in response to TH1 cells and antigen: responsiveness can be restored by IL-4.
Authors: Stevens T L , Vitetta E S 
Published: December 2022

Abstract
The ability of Th cells, type 1 (TH1), to activate and induce differentiation of B cells into antibody-secreting cells is controversial because 1) some clones of TH1 cells provide help while others do not, and 2) by using the same TH1 clone, different laboratories disagree on whether they provide help to B cells. One possible explanation for the latter is the variability in the activation status of the B cells used in different laboratories. In the present studies, we have used Ag-specific B cells from athymic (nu/nu) mice, or sterilely housed nu/+ mice to study the TH1-mediated activation of B cells that had received little or no prior help from T cells and/or antigen in vivo. These B cells express low levels of surface Ia (sIa) Ag, and fail to secrete IgG2a in response to TH1 cells plus Ag; in contrast, responses to TH2 cells plus Ag are normal. To explore this observation further, we prepared "surface(s) Ia1o" B cells from conventionally housed BALB/c mice by sorting spleen cells on the fluorescence-activated cell sorter. This sIalo population also failed to produce IgG2a in response to TH1 cells plus Ag. In contrast, the sIahi, (presumably more mature) B cells, responded to both the TH1 and TH2 cells. The addition of LPS, TH2 cells or the lymphokine, IL-4, to cultures of sIalo B cells from normal or nu/nu mice (plus Ag and TH1 cells), restored IgG2a responses to control levels. Low sIa levels were not the sole cause of nonresponsiveness of the nu/nu B cells because a 24-h pulse with IL-4 restored sIa to control levels without restoring IgG2a production after activation with TH1 cells plus Ag. These data support the conclusion that sIalo B cells are immature and require an activation/maturation signal from IL-4 in vivo in order to respond to TH1 cells and Ag in vitro.
Murine Thy-1+ dendritic epidermal cells induce immunologic tolerance in vivo.
Authors: Welsh E A , Kripke M L 
Published: December 2022

Abstract
To study the potential immunologic functions of murine Thy-1+ dendritic epidermal cells (Tdec), we used long term, IL-2-dependent, Tdec lines derived from the skin of C3H mice. Cells of the Tdec lines AU16 or AU4 were conjugated in vitro with the hapten FITC and injected s.c. into the footpad (ifp.) or i.v. into syngeneic recipient mice to assess their ability to induce or inhibit contact hypersensitivity (CHS). FITC-conjugated Tdec were unable to induce CHS after ifp. or i.v. injection. Furthermore, when mice were sensitized epicutaneously with FITC after the injection of FITC-conjugated Tdec, they were unable to mount a CHS response. These results indicated that hapten-conjugated Tdec are capable of inducing tolerance upon ifp. or i.v. injection. In contrast, ifp. injection of normal lymphocytes conjugated with FITC in vitro produced no impairment of the CHS response to FITC, although i.v. injection of these cells, as with that of FITC-conjugated Tdec, induced down-regulation of CHS. The immunologic tolerance induced by FITC-conjugated Tdec was Ag specific, but not H-2 restricted. Immunization with unconjugated Tdec either ifp. or i.v. did not induce tolerance, indicating that unconjugated Tdec by themselves are not suppressive. In addition, Tdec were unable to mediate a local graft-vs-host reaction in an F1 host. These results demonstrate that Tdec can induce immunologic tolerance and suggest that these cells may play a role in the down-regulation of cutaneous immune responses.