bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of the protective epitopes on the glycoproteins of Venezuelan equine encephalomyelitis virus by passive transfer of monoclonal antibodies.
Authors: Mathews J H , Roehrig J T 
Published: December 2022

Abstract
We have previously characterized seven unique antigenic epitopes on the two envelope glycoproteins of the Venezuelan equine encephalomyelitis (VEE) virus vaccine strain, TC-83, by using monoclonal antibodies. The in vitro function of virus neutralization was primarily associated with one epitope on the gp56 (gp56c). To determine which epitopes were important in protecting animals from VEE infection, purified monoclonal antibodies were inoculated i.v. into 3-wk-old Swiss mice. Twenty-four hours later these animals were challenged i.p. with 100 IPLD50 of virulent VEE virus (Trinidad donkey). High-avidity anti-gp56c, anti-gp50b, anti-gp50c, and anti-gp50d monoclonal antibodies protected animals from virus challenge. Rabbit antisera to the gp56 and the gp50 glycoproteins were also effective in protecting mice from challenge with virulent VEE virus. Less antibody was needed to protect animals if the antibody was directed against the critical neutralization site. Less avid antibodies to the gp56c and gp50b epitopes demonstrated little or no protection in vivo. Protection, therefore, appeared to be a function of the passive antibody's specificity, avidity, and ability to bind to virion antigenic determinants topologically proximal to the critical neutralization site.
Depression of natural killer activity and mitogen responsiveness in mice treated with pristane.
Authors: Freund Y R , Blair P B 
Published: December 2022

Abstract
In BALB/c mice, the injection of pristane resulted in a severe decrease in splenic T and B cell proliferative responses to mitogens and in a depression of natural killer (NK) activity. The effects of T and B cells, which persisted for at least 5 mo, were mediated by different mechanisms. T cell responsiveness to PHA dropped significantly below control levels 1 wk after the first of three monthly pristane injections, whereas B cell proliferation in response to LPS did not decrease until 4 wk after the first injection. The removal of plastic-adherent suppressor cells completely restored T cell proliferative capacity, but had no effect on B cells. NK activity against YAC-1 tumor targets was reduced 1 mo after the first pristane injection and remained depressed for at least 3 mo. This depression was not mediated by plastic-adherent suppressor cells. Spleen cell NK activity from pristane-treated mice could not be augmented by the interferon inducer Poly I:C to the same extent as that of control mice. This suggests an effect of pristane on either pre-NK cells or on cells that regulate NK activity.
Cell surface phenotype of a cloned line of human natural killer cells.
Authors: Kornbluth J , Flomenberg N , Dupont B 
Published: December 2022

Abstract
A human cell line with strong natural killer (NK) activity lacking alloreactive cytotoxicity was derived from a primary mixed lymphocyte culture (MLC). The line was developed from a single colony grown in soft agarose and subsequently expanded in liquid culture. Several subcultures with identical reactivity were established, one of which (3.3) was studied in detail. The morphologic and phenotypic characteristics of this line were distinct from those of alloreactive T lymphocytes. While reacting with a moAb to the sheep red blood cell receptor, it lacked the well-defined pan T cell markers Leu 1 and Leu 4, as well as the markers associated with functional T cell subsets Leu 2a and Leu 3a. Further morphologic, histochemical, and phenotypic characterization revealed this cell line to be strikingly similar to the larger granular lymphocyte (LGL) population, which contains the bulk of the natural killer cell activity normally found in peripheral blood. Cold target blocking studies confirmed the NK specificity of the observed cytotoxicity. Although unlabeled NK targets readily inhibited cytotoxic activity, B-LCL bearing the stimulating antigens of the original MLC failed to inhibit lysis of NK-sensitive targets. The growth of 3.3 was strictly dependent on IL 2 CM. Absorption studies with IL 2-dependent T cells and 3.3 revealed that both of these cell populations were equally effective in removing the growth-promoting factor(s) from IL 2 CM. These data suggest that at least some of MLC-generated NK activity is mediated by a population of cells similar to if not identical to LGL. These cells, in addition, appear to depend on the same growth-promoting factor(s) in IL 2 CM as do classical T lymphocytes.
Development of natural killer cell function in the human fetus.
Authors: Uksila J , Lassila O , Hirvonen T , Toivanen P 
Published: December 2022

Abstract
NK cell activity of four human premature infants between 28 and 33 wk of gestation and eleven human fetuses at 9 to 22 wk of gestation was tested against the K-562 cell line in a 4-hr 51Cr-release assay. Cord blood lymphocytes from premature infants expressed well-developed NK capacity, although the level of cytotoxicity was lower than that of full-term newborns or adults. Cells prepared from fetal liver displayed cytotoxicity against K-562 targets in four out of eleven fetuses, whereas cells from fetal bone marrow, spleen, and thymus expressed only marginal or negative anti-K-562 killing. NK cell activity in the fetal liver was observed as early as at 9 wk of gestation. The functional NK capacity of premature infants and fetuses was augmented in vitro by IFN-alpha treatment. Fetal cells without spontaneous NK activity did not develop cytotoxicity against K-562 target cells in the presence of IFN-alpha. The present results corroborate the concept of the intrauterine development of human NK cell activity.
Identification and partial purification of a B cell growth-promoting material utilizing the BCL1 cell line.
Authors: Thoman M L , Weigle W O 
Published: December 2022

Abstract
A B cell growth-promoting factor (BCGF) can be detected in the culture supernatants of activated murine and human spleen cells, human peripheral blood lymphocytes, and a murine thymoma cell line by the use of the B cell leukemic cell line BCL1, which is induced to proliferate in response to this factor. Although this BCGF stimulates BCL1 cells to proliferate, it is not mitogenic for resting B cells but synergizes with dextran sulphate to induce proliferation of the latter cells. This factor has no T cell-replacing activity in an antibody response. BCGF co-purifies with interleukin 2 (IL 2) by gel chromatography and isoelectric focusing but can be separated by phenyl-Sepharose chromatography.
In vitro immunization to KLH. II. Limiting dilution analysis of antigen-reactive cells in primary and secondary culture.
Authors: Gebel H M , Scott J R , Parvin C A , Rodey G E 
Published: December 2022

Abstract
Limiting dilution analysis was used to estimate the frequency of human peripheral blood T lymphocytes that proliferate in response to in vitro immunization with keyhole limpet hemocyanin (KLH). Antigen-reactive cells (ARC) were estimated 9 days after primary immunization with KLH. The ARC frequency of lymphocytes from 12 subjects ranged from 1:23,800 to 1:52,631. Lymphocytes from five of these subjects were also primed for 12 days with KLH, rechallenged in secondary culture with fresh adherent cells and KLH, and assayed 4 days later. The ARC frequency increased to 1:1,123 to 1:7,247, indicating that T cell clones responsive to KLH had expanded during primary culture. In addition, we observed that the proliferative response of lymphocytes from 5 of the 12 subjects were inhibited at high cell concentrations. Depletion of OKT8+ T cells before culturing with KLH however did not alter the inhibitory effect of high concentrations of T cells.
Evidence for beta 2-microglobulin-like and H-2-like antigenic determinants in Drosophila.
Authors: Shalev A , Pla M , Ginsburger-Vogel T , Echalier G , Lögdberg L , Björck L , Colombani J , Segal S 
Published: December 2022

Abstract
Serologic evidence for the existence of beta 2-microglobulin-, (beta 2m) like and H-2-like antigenic determinants in Drosophila are presented. Drosophila-cultured cells and larvae extract were shown to react specifically with a rabbit anti-rat beta 2m and a rabbit anti-mouse beta 2m antisera. G-200 pooled fractions from Drosophila larvae were shown to react with beta 2m-eluted and glycin-absorbed antisera, but not with beta 2m-absorbed or glycin-eluted antisera. These fractions also quantitatively inhibited the heterologous reaction between the anti-beta 2m antisera and purified human and rat beta 2m. The lack of reactivity of other rabbit antisera or normal serum with Drosophila, as well as the efficiency of absorption of anti-beta 2m reactivity by either rat or KCO% (Drosophila) cells, further supports the presence of beta 2m epitopes on Drosophila cells. Data are also presented showing that certain anti-H-2 alloantisera react with Drosophila. That this reactivity is indeed due to anti-H-2 antibodies is suggested by several lines of evidence, including the removal of cytotoxic alloantibodies and lack of reactivity by other mouse antisera and monoclonal reagents. Preliminary data suggest that the H-2-like and beta 2m-like determinants are physically associated on the cell surface of Drosophila cells. These findings have important implications on current concepts concerning the evolutionary origin and physiologic role of beta 2m and the major histocompatibility complex.
Studies on the cellular nature of Candida albicans-induced suppression.
Authors: Rivas V , Rogers T J 
Published: December 2022

Abstract
Animals treated with formalinized Candida albicans manifest depressed cellular immune activity. Splenocytes from mice treated with as little as 14 micrograms of this material exhibited significantly reduced responses to the T cell-dependent mitogens phytohemagglutinin and concanavalin A. On the other hand, the B lymphocyte-dependent response to bacterial lipopolysaccharide was normal in these cultures. Splenocytes from treated mice were capable of actively suppressing the T cell- (but not B cell-) dependent proliferative response of normal cells. Analysis of splenocytes from Candida-treated mice showed that the suppressor cell is adherent to glass wool, is not adherent to Sephadex G-10, does not phagocytize carbonyl iron, is not susceptible to treatment with anti-Thy-1 plus C, but does bind specifically to anti-immunoglobulin- (anti-Ig) coated dishes. The adherence to the anti-Ig-coated dishes was not due to the simple attachment of Fc receptor-bearing lymphocytes, because dishes coated with the F(ab')2 fragment of rabbit antimouse IgG bound the suppressor cell. These results suggest that the active Candida-induced suppressor cell is composed, at least in part, of surface Ig-bearing B lymphocytes.
Allotype-defined mRNA for rabbit immunoglobulin H and L chains isolated from rabbit-mouse hybridomas.
Authors: Dreher K L , Sogn J A , Gates F T , Kuo M C , Kindt T J 
Published: December 2022

Abstract
Improved procedures have expedited the formation and propagation of stable rabbit-mouse hybridomas (RMH) that secrete rabbit immunoglobulin (Ig) chains and that serve as sources for allotype-defined mRNA, specifying both constant and variable regions of rabbit Ig. The Ig-secreting hybridomas were stabilized by multiple recloning steps and eventually attained a 90% frequency of cells secreting rabbit Ig chains. Stabilized RMH were propagated in vivo in nude (athymic) and in some instances in conventional BALB/c mice. Rabbit Ig products secreted by these RMH cell lines were isolated and were shown to have amino acid sequence characteristics of rabbit Ig chains and that are distinct from those of the mouse. Preparative amounts of polyadenylated RNA-(poly(A) RNA) encoding allotype-defined rabbit Ig chains were isolated from RMH grown as solid tumors. Poly(A) RNA encoding a b4 L chain from one RMH (12F2) and an a3 H chain from another (7D2) were purified 10-fold by sucrose density gradient centrifugation and were characterized in an in vitro translation system. The mRNA encoding the b4 allotype had an S value of 12 and directed the synthesis of a rabbit precursor L chain with m.w. 27,500. Radiochemical amino acid sequence analysis of the L chain precursor has shown it to include a 22 residue leader sequence with a leucine profile similar to that of murine L chain precursors. Analysis of the mRNA encoding the a3 H chain revealed it has an S value of 16 and directed the synthesis of an Ig chain with a m.w. identical to that of the rabbit H chain secreted by the RMH.
Stimulation of secondary anti-MSV cytolytic T lymphocytes with MBL-2 reconstituted membranes.
Authors: Duprez V , Mescher M F , Burakoff S J 
Published: December 2022

Abstract
Membranes and solubilized, reconstituted membranes from Moloney-infected tumors MBL-2 have been used to stimulate in vitro secondary cytolytic T lymphocytes (CTL) in C57BL/6 mice primed and Moloney murine sarcoma virus. Membranes are shown to stimulate the generation of Moloney-specific and H-2 restricted CTL. Stimulation with solubilized, reconstituted membranes required the presence of rat lymphocyte Con A supernatant (containing interleukin 2) during the culture. Reconstituted membranes made in the presence of the detergent-insoluble fraction from the plasma membrane were able to stimulate a response in the absence of Con A supernatant.
The extent of self-MHC restriction of cytotoxic T cells in nude mice varies from mouse to mouse.
Authors: Miller R G , Derry H R , Sarjeant B J 
Published: December 2022

Abstract
There are conflicting results as to whether the response of athymic nude mice to TNP-modified self determinants is or is not H-2 restricted. We cultured spleen cells from 29 individual RNC (H-2k) nude mice with TNP-modified self determinants and tested the cultures for their ability to lyse TNP-modified self (RNC-TNP) and TNP-modified allogeneic (BALB/c-TNP) target cells. Each mouse was stimulated by two different protocols: either by the addition of TNP-modified irradiated nu/+ spleen cells or by TNP modification of the nude responder cells without addition of other cells. All mice could lyse RNC-TNP targets and about one-half could also lyse BALB/c-TNP targets, i.e., there was a 50:50 division between restricted and unrestricted responses. The magnitude of the response against RNC-TNP and whether the response was restricted were both independent of the method of stimulation. We conclude that H-2 restriction in these mice is imposed by an as yet unidentified environmental influence that can vary from one nude mouse to the next. The influence appears to act through negative selection because the modified self response is, if anything, higher in mice showing an unrestricted response.
Role of self carriers in the immune response and tolerance. VIII. Suppression of the MOPC-104E idiotypic response by idiotype-modified self, but not by dextran-modified self.
Authors: Grouix B , Scott D W 
Published: December 2022

Abstract
We have investigated the suppression of the anti-dextran B1355S immune response using our model of modified self. The anti-dextran response is idiotypically well defined in BALB/c mice. This system enables us to examine the contribution of various predominant idiotypes to the antibody response under conditions of suppression by antigen or by idiotype-specific suppressor cells. Our results demonstrate that the total anti-dextran response can be inhibited by pretreatment of animals with dextran-coupled syngeneic spleen cells; however, the representation of major idiotypes constituting this response are not reduced in percentage. In contrast, pretreatment of mice with MOPC-104E-coupled spleen cells leads to a specific suppression of the private IdI-104E idiotype. The total anti-dextran response remains unchanged, as well as proportions of other major idiotypes known (IdI-588 and IdX). This suppression is mediated by Thy-1.2+, Lyt-2.2+ T cells, as demonstrated by adoptive transfer assays. This system will allow the molecular dissection of the regulation of an idiotypically well-defined system for the suppression by either antigen- or idiotype-specific suppressor T cells.
Immune response to the p-azobenzenearsonate (ABA)-GAT conjugate. II. Hapten-specific T cells induced with ABA-GAT in GAT responder X nonresponder F1 hybrids are restricted to the nonresponder haplotype.
Authors: Regnier D , Seman M 
Published: December 2022

Abstract
Immunization of mice with the ABA-GAT conjugate stimulates GAT-specific T helper cells in GAT-responder animals and ABA-specific helpers in nonresponders. Unexpectedly, immunization of (responder X nonresponder) F1 mice, which have the GAT-responder phenotype, leads to the recruitment of both ABA- and GAT-specific clones of T helper lymphocytes. The GAT-reactive population is restricted to the haplotype of the responder parent (Iak), whereas ABA-specific T cells are mostly restricted to the nonresponder one (Ias). This is demonstrated by the ability of monoclonal antibodies to parental la antigens to inhibit T cell proliferation to GAT or ABA-Tyr in vitro. Consistently, ABA-GAT-primed F1 T cells can only activate nonresponder B cells to proliferate in the presence of ABA-Tyr and responder B lymphocytes in the presence of GAT. Furthermore, F1 T cells seem to recognize both ABA and GAT epitopes only in association with molecules encoded by the I-A subregion. Analysis of ABA-specific F1 T cell lines generated by in vitro stimulation with ABA-Tyr or ABA-GAT demonstrates a competition between GAT- and ABA-specific T cells present in the hybrid T cell repertoire and restricted to the same parental I-Ak molecule. The results indicate that F1 macrophages can present both ABA and GAT epitopes to T cells in association with the two parental and hybrid Ia determinants. It seems unlikely that the absence of GAT-specific T cells restricted to the nonresponder I-A in the F1 is due to suppressor T cells. Thus, the competition model that we propose, to explain the selective F1 T cell response to ABA-GAT, leads us to believe that GAT nonresponder animals may lack clones capable of recognizing, with a high affinity, I-As + GAT.
Hapten-specific T cell response to azobenzenearsonate-N-acetyl-L-tyrosine in the Lewis rat. III. Effects of peptide-spacer structure on eliciting ABA-specific helper activity with TNP-haptened ABA-peptide-Ficoll.
Authors: Komatsu T , Lawn C Y , Amsden A , Leskowitz S 
Published: December 2022

Abstract
A series of antigens was synthesized in which peptide spacers were inserted between the ABA group and TNP-Ficoll. When these antigens were used to assess helper activity in Lewis rats immunized with ABA-tyr, it was found that an increase in the ABA-epitope density and an increase in the peptide spacer size both increased the efficacy of the antigen in eliciting ABA-specific help, manifest by an enhancement of anti-TNP PFC. Substitution of D- for L-amino acids progressively decreased the ability of these conjugates to elicit help until D-tyr-D-ala-D-ala, which when used for coupling ABA to the TNP-Ficoll resulted in a nonimmunogenic molecule. When these same Ficoll conjugates were used to study ABA-specific in vitro proliferative responses, it was found that introduction of even a single D-amino acid into the spacer greatly reduced reactivity. By contrast the ABA-peptides, free of the Ficoll backbone, were all equivalent on a molar basis in their ability to elicit ABA-specific in vitro proliferation, regardless of their content of D-amino acids. These results suggest some form of digestion is required in the processing of these antigens before they can elicit helper activity. This processing can occur only if one or more L-amino acid residues are present. If the ABA-peptides are free of the Ficoll backbone, they are all capable of stimulating T cell proliferation without apparent further processing.
Activation of antigen-enriched B cells. II. Role of linked recognition in B cell proliferation to thymus-dependent antigens.
Authors: Snow E C , Noelle R J , Uhr J W , Vitetta E S 
Published: December 2022

Abstract
The responsiveness to T-dependent (TD) and T-independent (TI) TNP-antigens of murine splenic B cells previously enriched for antigen-binding cells (ABC) was examined. TNP-TI antigens induced B cell proliferation. TNP-TD antigens did not induce a proliferative response regardless of the physical form or nature of the TNP-TD antigen (e.g., soluble vs particulate, low or high haptenation of carrier, TNP on various insoluble matrices, etc.). TNP-TD antigens were effective in enhancing the response of the TNP-ABC to all concentrations of lipopolysaccharide (LPS) tested, indicating that binding of antigen to surface immunoglobulin alters the LPS responsiveness of the cell. Irradiated, keyhole limpet hemocyanin- (KLH) primed T cells induced a threefold to fourfold greater B cell proliferative response with TNP-KLH than with fluoresceinated KLH (FLU-KLH) or FLU-KLH together with TNP-human serum albumin (TNP-HSA). Therefore, linked recognition appears essential for optimal T cell-mediated B cell proliferation, whereas the induction of B cell proliferation via nonlinked, carrier-activated T cells is a minor component of the response.
Selective activation of antigen-specific human B cells in recently immunized individuals by nonspecific factors in the absence of antigen.
Authors: Peters M , Fauci A S 
Published: December 2022

Abstract
The in vitro effect of nonspecific factors (derived from mixed lymphocyte culture [MLC] supernatants) on human B cell responses was studied in individuals recently immunized in vivo to keyhole limpet hemocyanin, tetanus toxoid, and/or diphtheria toxin. In T cell-depleted fractions of peripheral blood mononuclear cells, nonspecific factors alone, without antigen, selectively induced a specific antibody response to the antigen to which the individual had been recently immunized, at dilutions that did not generate a significant polyclonal response in the remainder of the B cell repertoire. The source of these factors, with respect to MLC donors, did not affect the antibody response. Supernatants of MLC from nonimmunized individuals induced a specific antibody response as effectively as supernatants of MLC from immunized individuals, when added to B cells plus monocytes from recently immunized individuals. Studies in which the same individuals were followed over time showed that these factor-sensitive B cells are seen in the peripheral blood of recently immunized individuals for only a finite period of time. Thus, in vivo immunization with a specific antigen results in the transient appearance in the peripheral blood of B cells that are specific for the antigen in question. These B cells are probably preactivated in that nonspecific factors selectively induce in vitro their further differentiation into antibody-secreting cells, in the absence of added antigen or mitogen. These studies may add further insight into our understanding of the sequential steps involved in the activation and differentiation of human B lymphocytes and provide a model for the combined in vivo and in vitro study of human B cell physiology.