bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel role for macrophages: the ability of macrophages to tolerize B cells.
Authors: Phipps R P , Scott D W 
Published: December 2022

Abstract
We investigated the ability of macrophages (M phi) to present the tolerogen fluoresceinated sheep gamma-globulin (FL-SGG) to B cells. M phi pulsed with FL-SGG or murine FL-IgG2 were able to tolerize normal spleen B cells specifically as assessed by the plaque-forming cell (PFC) response to the antigens FL-Brucella abortus (FL-BrA) and FL-polymerized flagellin (FL-POL). Tolerance was not induced when M phi were pulsed with a variety of other FL antigens or the synthetic tolerogen FL-D-glutamic acid-D-lysine (FL-D[G,L]). The ability of M phi to tolerize B cells was not T cell-dependent, because populations of both T-depleted B cells and hapten-specific B cells were tolerizable. M phi-induced B cell tolerance did not exhibit genetic restriction with regard to the H-2 haplotype of the presenting M phi or the responding B cells. A variety of different types of peritoneal M phi, including normal resident M phi and those elicited by thioglycollate or concanavalin A (the latter are predominantly la+), could tolerize B cells after being pulsed with FL-SGG. We compared tolerogen-pulsed M phi to soluble tolerogen for the ability to tolerize B cells and found that tolerogen bound to M phi was more than 10 times as potent as an equivalent amount of soluble tolerogen. In contrast to the ability of M phi to present FL-SGG in a tolerogenic fashion to B cells, the P388AD lymphoid dendritic cell-like tumor line presented FL-SGG in an immunogenic mode to B cells. Tolerogen bound to P388AD cells could specifically augment a PFC response to both FL-BrA and FL-POL. We suggest that certain types of M phi may play a role in unresponsiveness by enhancing the tolerogenicity of soluble antigen, whereas other accessory cells may present the same moieties in an immunogenic fashion.
Generation of autoreactive cytotoxic T lymphocytes under limiting dilution conditions.
Authors: Reimann J , Miller R G 
Published: December 2022

Abstract
The ability of F1 (H-2k/d) responder cells to generate cytotoxic effector cells against parental and F1 targets was investigated under limiting dilution conditions. One hit limiting dilution curves, consistent with the generated cytolytic cells being the progeny of a single precursor cell, were reproducibly obtained if a culture was scored as "responding" on the basis of its ability to lyse one or more of a panel of Con A blast targets consisting of self F1 and both parents. The calculated frequency of the precursor cell in a nylon wool-nonadherent splenic responder cell population ranged from about 1/500 to 1/1600 in (B10.BR X B10.D2)F1 and (RNC X BALB/c)F1 mice. The patterns of lysis expressed by individual microcultures against the panel of F1 and both parental targets were unusual; besides patterns that were consistent with predictions of classic transplantation rules (i.e., lysis of F1 targets plus one/both parental targets), "anomalous" patterns (i.e., lysis of F1 targets or one/both parental targets exclusively) were also seen. The precursor cells that gave rise to cytolytic cells were devoid of T cell markers, whereas the cytolytic effector cells were Thy-1+, Lyt-2+, as defined by sensitivity to treatment with monoclonal antibody plus complement. The data are discussed in the context of early in vitro development of cytolytic T lymphocytes, with particular emphasis on a possible manifestation of an early T cell repertoire.
Characterization of determinants encoded by four Qa-1 genotypes and their recognition by cloned cytotoxic T lymphocytes.
Authors: Jenkins R N , Rich R R 
Published: December 2022

Abstract
The alloantigens encoded by the four defined Qa-1 genotypes were characterized by cloned cytotoxic T lymphocyte (CTL) recognition. CTL clones specific for Qa-1a- and for Qa-1b-encoded antigens were generated. Examination of the reactivity of these clones with target cells from H-2r and H-2f strains provided the strongest evidence to date for the designation of the Qa-1c and Qa-1d genotypes, respectively, for these strains. Qa-1c-encoded antigens were recognized by most, but not all CTL clones that specifically lysed Qa-1b target cells, thus demonstrating that these antigens lack a Qa-1b-associated determinant. Similarly, Qa-1d encoded antigens were recognized by only half of the CTL clones that lysed Qa-1a target cells. In addition, one CTL clone that was cytotoxic for Qa-1b and Qa-1c target cells demonstrated low affinity, cross-reactive recognition of a Qa-1d encoded antigen. The reactivity patterns of the monoclonal CTL defined five Qa-1 determinants. Qa-1a, Qa-1b, and Qa-1d each encode multiple determinants. Two Qa-1d encoded determinants probably reside on different molecular species. Finally, large numbers of CTL clones tested on panels of target cells indicated that the Qa-1a strains expressed indistinguishable Qa-1.1 antigens and the Qa-1b strains expressed indistinguishable Qa-1.2 antigens. Therefore, additional polymorphism among these strains is improbable.
Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines.
Authors: Wilde D B , Marrack P , Kappler J , Dialynas D P , Fitch F W 
Published: December 2022

Abstract
Monoclonal antibody GK1.5 recognizes a determinant, designated L3T4a, on the murine T cell surface molecule L3T4. The expression of L3T4a by functional murine T cell clones appears to correlate primarily with class II MHC antigen reactivity rather than with functional phenotype. In previous studies, antigen-specific cytolysis by a cloned class II MHC antigen(I-Ak)-reactive CTL line was found to be blocked entirely by monoclonal antibody (mAb) GK1.5, at a step before the lethal hit. In the present studies, we demonstrate that mAb GK1.5 profoundly blocks antigen-specific proliferation and release of lymphokines by cloned murine class II MHC antigen-reactive helper T lymphocyte (HTL) lines. Analysis of cloned T cell hybridomas, however, suggests that there exists clonal heterogeneity in the degree of inhibition of class II MHC antigen-specific function by mAb GK 1.5. Finally, we present evidence that mAb GK1.5 blocks class II MHC antigen-specific function by blocking class II MHC antigen-specific binding. The data presented here lend considerable support to the concept both that L3T4 and the human Leu-3/T4 molecules are similar and that L3T4 plays a role in class II MHC antigen-reactivity by murine T cells.
Studies on the immunogenicity and tolerogenicity of T-independent antigens.
Authors: Dintzis R Z , Middleton M H , Dintzis H M 
Published: December 2022

Abstract
The T-cell independent immunological responses of naive mice to a series of size-fractionated dinitrophenylpolyacrylamide molecules were measured. These responses were correlated in vitro and in vivo with hapten number per molecule and hapten density per unit length. We found that to be immunogenic, a T-independent molecule must contain a threshold number (approximately 20) of appropriately spaced haptens or epitopes. We infer that this condition is necessary for simultaneous B-cell receptor binding and clustering. Molecules with less than this number of haptens are not immunogenic at any dose. Some nonimmunogenic molecules are capable of inhibiting the response to the immunogenic ones; this capability increases with increasing hapten density. In order for a molecule to accommodate 20 or more appropriately spaced haptens, it must be above a threshold size. Increasing hapten density in a molecule at or above threshold size and hapten number increases its immunogenicity. Increasing hapten density in a molecule below threshold size increases its tolerogenicity. Conclusions concerning immunogenicity and tolerogenicity of T-independent antigens may not be warranted unless the molecular weight and hapten or epitope number per molecule are well characterized.
The use of haptenated immunoglobulins to induce B cell tolerance in vitro. The roles of hapten density and the Fc portion of the immunoglobulin carrier.
Authors: Waldschmidt T J , Borel Y , Vitetta E S 
Published: December 2022

Abstract
The relationship between the Fc region of trinitrophenylated (TNP)-immunoglobulins (Ig), and their ability to induce tolerance was examined. It was found that adult B cells responding to a T-independent (TI) antigen were tolerized by TNP11 human gamma globulin (HGG), but not by TNP10F(ab')2 fragments of HGG. Increasing the hapten density on the F(ab')2 fragments overcame their inability to induce tolerance. Thus, a TNP17-F(ab')2 was an effective tolerogen. Murine myeloma proteins of different IgG subclasses were similarly tested. A TNP12-IgG2a and a TNP11-IgG1 induced tolerance, whereas two TNP11-12-IgG3 did not. However, a more heavily haptenated TNP18-IgG3 was tolerogenic. These results suggest that lightly haptenated immunoglobulins depend upon Fc receptor binding to induce tolerance in adult B cells. Non-Fc receptor-binding carriers are not tolerogenic unless they are more heavily haptenated. Finally, T cell and macrophage depletion experiments suggest that the tolerogens act directly on the B cells.
Limiting dilution analysis of alloreactive cytotoxic precursor cells in aging mice.
Authors: Nordin A A , Collins G D 
Published: December 2022

Abstract
The quantitative minimal estimate of the frequency of alloantigen specific cytotoxic T lymphocyte precursor cells (CTL-p) was determined in young and old C57BL/6 mice by limiting dilution analysis. Supernatant from phorbol myristate acetate-induced EL-4 cells was used as a source of IL 2 in these assays, which therefore were independent of the presence of the Lyt-2-, IL 2-producing cells known to be deficient in aging mice. These studies showed that 24-mo-old mice had approximately 10-fold fewer CTL-p than their young counterparts. Comparison of the limiting dilution assay (LDA) with IL 2-supplemented primary MLC shows that estimates of the frequency of CTL-p do not consistently agree with cytotoxic activity detected in the higher cell density primary MLC, and that the LDA is most likely a better estimate of the effect of age on the development of CTL.
B lymphocyte lineage cells in newborn and very young NZB mice: evidence for regulatory disorders affecting B cell formation.
Authors: Jyonouchi H , Kincade P W , Good R A , Gershwin M E 
Published: December 2022

Abstract
As adults, NZB mice have a severe deficiency of identifiable precursors of B lymphocytes, but this is preceded by a time when B cells and their immediate precursors are present in bone marrow in elevated numbers. Our present studies indicate that the final stages of B cell formation may be proceeding at a greater than normal rate at 4 wk of age. At this time, large numbers of sIg- B cell precursors can be identified in NZB but not in normal CBA/H or DBA/2 marrow that can respond to mitogens in semisolid agar cultures without preculture. Colony formation by these precursors was dependent on the presence of Sephadex G-10-adherent cells in the suspensions. In this respect, 4-wk-old NZB marrow was similar to spleen and liver of normal CBA/H newborn mice. Mixing experiments suggested that hyperactive regulatory cells present in young NZB marrow may promote functional maturation of normal pre-B cells from CBA/H or DBA/2 mice. In addition, potent substances present in the serum of young but not older NZB mice produced the same effect. Factor-mediated enhancement of clonal proliferation by sIg- precursors was not dependent on adherent cells and required more than brief exposure of the cells to young NZB serum. These are all indications that abnormalities of B lineage differentiation in young NZB marrow may be attributable to microenvironmental elements. Congeneic, B cell-deficient NZB.xid mice, however, lacked hyperactive regulatory cell function and serum factors that characterize NZB mice of this age. A study was also made of B cell precursors in newborn spleen and liver of NZB mice, and abnormal shifts of populations of B lineage cells were already present by that time. These observations support previous contentions that humoral immunity is precocious and abnormally regulated in NZB mice.
Dissociation of autologous and allogeneic mixed lymphocyte reactivity by using a monoclonal antibody specific for human T helper cells.
Authors: Ellis T M , Mohanakumar T 
Published: December 2022

Abstract
A monoclonal antibody defining a population of human T helper cells was developed and shown to specifically block the autologous mixed lymphocyte reaction (AMLR). This antibody, termed KT69-7 (IgG1), recognized 62% of peripheral blood E rosette-positive (E+) cells while demonstrating negligible reactivity with E- cells, monocytes, granulocytes, EBV-transformed B cell lines, and mouse splenocytes. Separation of E+ cells into KT69-7+ and KT69-7- populations revealed that KT69-7+ T cells provided helper function in PWM-driven B cell differentiation, whereas KT69-7- T cells provided no help and may suppress this response. Modulation of membrane moieties by using KT69-7 or OKT4 plus goat anti-mouse IgG removed reactivity to both these antibodies, suggesting an association between these molecules recognized by these antibodies. In functional studies, KT69-7 selectively blocked the AMLR while demonstrating minimal or no effect on the allogeneic MLR (allo-MLR). Blocking of the autoreactivity occurred when either autologous B lymphocytes or macrophages were used as stimulators. The failure of KT69-7 to block the allo-MLR was not attributable to excessive allogeneic stimulus; KT69-7 failed to block even under conditions of limiting numbers of stimulator cells. KT69-7 thus appears to recognize a molecule on the surface of T helper cells required for recognition of autologous class II antigens.
Induction of human gamma interferons by a mitogen derived form Mycoplasma arthritidis and by Phytohemagglutinin: differential inhibition with monoclonal anti-HLA.DR antibodies.
Authors: Cole B C , Thorpe R N 
Published: December 2022

Abstract
The peripheral blood lymphocytes from eight healthy volunteers produced significant amounts of interferon (IFN) when co-cultured with a recently discovered mitogen preparation derived from cultures of Mycoplasma arthritidis (MAS). Maximum levels of 281 to 2187 U were reached after 3 to 4 days of incubation. The IFN was characterized as IFN gamma on the basis of pH and heat lability, and neutralization with anti-human IFN gamma but not anti-IFN alpha. A monoclonal antibody to HLA.DR determinants suppressed IFN induction and lymphocyte proliferation when co-cultured with MAS but was not effective against PHA-induced IFN and proliferation; PHA-induced proliferation was enhanced in the presence of the antibody. Anti-HLA.DR-mediated inhibition of lymphocyte functions, however, was not specific for MAS inasmuch as viral-induced IFN was also suppressed, as was Con A-induced proliferation. These and other studies suggest that the cellular requirement for T cell activation by MAS, PHA, and Con A may all be distinct.
T cell nature and heterogeneity of recognition structures of human natural killer (NK) cells.
Authors: Fast L D , Beatty P , Hansen J A , Newman W 
Published: December 2022

Abstract
Very low doses of trypsin (5 micrograms/ml) are sufficient to ablate NK cell activity. This finding was used to make several observations, and we have attempted to relate these observations to specific cell surface macromolecules. First, trypsinized effector cells no longer lysed seven different NK-susceptible targets, but the lysis of three additional targets was unaffected. These results suggest a heterogeneity of recognition potential that is inconsistent with the notion that there is only one class of NK "receptors" and one class of "target structures." Trypsin does not affect the conjugation of effector and target cells. Secondly, we have tried to identify those cell surface molecules that are affected by this low dose of enzyme. The examination of the 125I-labeled glycoprotein fraction NK-enriched cells showed that at least four molecules are cleaved, one of which may be in the T200 family. The examination of the [3H]galactose-labeled cell surface glycoproteins suggested in particular that some high m.w. glycoproteins were affected at the dose of trypsin that ablates NK function. Analysis of those molecules that we previously implicated in NK function, defined by monoclonal antibodies that block NK lysis, allowed us to rule out a role for the Tp 50 and Lp95-150 structures, while providing additional evidence of a role for the T200 glycoproteins in the trypsin-sensitive stage of cytolysis. Finally, closer examination of the electrophoretic mobilities and trypsin sensitivity of the T200 structures on highly enriched NK cells showed these structures to be indistinguishable from the T cell form of T200, yet quite distinct from the monocyte form. These results are therefore consistent with the possibility that NK cells are of the T rather than the monocyte lineage, and furthermore support a role for the T200 structure in the post-binding trypsin-sensitive stage of the NK cytolytic process.
Two-dimensional gel comparisons of murine H-2D region-associated antigens of different H-2 haplotypes.
Authors: Nichols E A , Krakauer T , Hansen T H 
Published: December 2022

Abstract
The heterogeneity of histocompatibility antigens encoded within the H-2D region of murine chromosome 17 was investigated in several mouse strains using monoclonal antibodies. Sequential immunoprecipitation and two dimensional gel electrophoresis (2D) were used to determine the number and structural relatedness of antigenically distinct products of the same H-2D region. Strikingly different, haplotype-specific patterns were observed. The three antigenically distinct molecules, Dd, Ld and Rd, all encoded within the Dd region, each showed a unique constellation of spots by 2D analysis, although the Ld and Rd molecules showed more structural similarity to each other than either molecule showed to the Dd molecule. Comparisons of the Ld and Rd molecules using sequential precipitations and a cloned Ld gene suggested that they are not conformation or glycosylation variants of the same polypeptide, implying they have different primary amino acid sequences. Using an anti-Ld antibody, the Ldml molecule was isolated from cells of the Dd region mutant mouse strain B10.D2-H-2dml and was found to have a 2D gel profile clearly distinguishable from the profile of either Ld or Dd molecules isolated from the wild-type strain B10.D2. Of the three antigenically-distinct molecules determined by the Dq region, the 2D gel profile of the Rq molecule was different from that of the Dq and Lq, the latter two molecules being indistinguishable. In contrast to these findings, analysis of the gene products of the Db region failed to resolve either antigenic or molecular heterogeneity and the multiple, antigenically distinct gene products of the Dw16 region were indistinguishable by 2D comparisons. These haplotype specific variations in the structural relatedness and number of antigenically distinct molecules determined by D region genes support the hypothesis that class I MHC genes are in a dynamic evolutionary state of gene expansion and contraction.
Primary structure of the variable region of a human lambda VI light chain: Bence Jones protein SUT.
Authors: Frangione B , Moloshok T , Solomon A 
Published: December 2022

Abstract
To ascertain if lambda VI light chains have unique structural features that account for the preferential association of these proteins with primary or multiple myeloma-related amyloidosis (amyloidosis AL) we have determined the complete amino acid sequence of the variable (V) region of the lambda VI Bence Jones protein SUT. This protein, obtained from a patient with amyloidosis AL, represents a complete light chain consisting of 216 residues and it has structural and serologic properties characteristic for lambda VI light chains. The sequence of the joining segment (J) (positions 100 to 111) of protein SUT is identical to that of the J lambda I segment of the mouse IG lambda light chain gene. V region SUT is closely homologous in sequence to that of another lambda VI amyloid fibrillar protein, AR, differing by 21 residues. The V regions of proteins SUT and AR contain a two-residue insertion at positions 68 and 69 that has also been found in two other lambda VI human light chains but not in the lambda-chains of other V region subgroups.
Isolated liver granulomas of murine Schistosoma mansoni contain components of the angiotensin system.
Authors: Weinstock J V , Blum A M 
Published: December 2022

Abstract
Angiotensin I (AI) and angiotensin II/III (AII/III) were detected by radioimmunoassay in homogenates of isolated liver granulomas from mice infected for 8 wk with Schistosoma mansoni. Angiotensin I converting enzyme (ACE) activity, which could be completely inhibited by captopril, a specific ACE inhibitor, was also present as determined by radioassay. Spontaneous angiotensin I-generating activity was detected in homogenates that received supplemental angiotensinogen (protein renin substrate). This activity was partly inhibited by pepstatin, an acid protease inhibitor, indicating the presence of angiotensinogenase(s). Trypsinization of homogenates resulted in some AI generation, which suggests that homogenates had AI precursor. Treatment of infected mice with MK421, another specific ACE inhibitor, decreased granuloma ACE activity and AII content and size. AII, and to a lesser extent AIII, inhibited mouse peritoneal macrophage migration in an in vitro assay. These data support the contention that components of the angiotensin system are in the granuloma and may serve a function in regulation of the inflammation.
Pre-B cells in mouse bone marrow: immunofluorescence stathmokinetic studies of the proliferation of cytoplasmic mu-chain-bearing cells in normal mice.
Authors: Opstelten D , Osmond D G 
Published: December 2022

Abstract
By using a technique that combines metaphase arrest with immunofluorescence labeling, the proliferation of specifically identified pre-B cells in mouse bone marrow has been analyzed under physiological conditions in vivo. Pre-B cells bearing cytoplasmic mu-chains and no surface mu-chains constituted 12% of marrow nucleated cells, or 27 X 10(5) cells/femur, whereas surface mu-bearing B lymphocytes totaled 33 X 10(5) cells/femur. Pre-B cells measured 7 to 14 micron in diameter, the small number seen in metaphase (1 to 2%) being large cells (greater than 10 microns). After vincristine injection, the metaphase incidence (Imet) of pre-B cells increased with cell size; a broad-dose range of vincristine gave similar Imet values. Mitoses were arrested for 4 hr with no apparent cell death. Linear regression analysis of the increase in Imet of pre-B cells 2 to 4 hr after vincristine revealed a rate of entry into mitosis of 6.3%/hr, relative to all pre-B cells (average compartment turnover time, 16 hr), and 15.3%/hr for the large proliferating pre-B cell subset. This represented a pre-B cell production of 1.3 X 10(5) cells/femoral shaft/hr or 0.5 X 10(8) cells/whole bone marrow organ/day, emphasizing the magnitude of B lymphocyte genesis in normal bone marrow. Combined with reported renewal rates for small pre-B cells and small B lymphocytes, these values form a kinetic model of B lymphocyte development. The results reveal an apparent overproduction of large pre-B cells, consistent with a speculative post-mitotic loss of some immature primary B lymphocytes.