bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell-induced Ig allotypic suppression in mice. II. Both CD4+ CD8- and CD4- CD8+ T cell subsets from sensitized Igha mice are required to induce suppression of Igh-1b allotype expression.
Authors: Benaroch P , Bordenave G 
Published: December 2022

Abstract
We established the phenotype of T splenocytes (Ts) from Igha/a BALB/c mice sensitized against B splenocytes from the Ighb/b CB20 congenic mice that induce Igh-1b (IgG2a of the Ighb haplotype) suppression. This was achieved by studying the action of anti-T cell subset mAb on the capacity of Ts to induce this chronic allotypic suppression in Igha/b (BALB/c x CB20)F1 mice. The Ts were treated with cytotoxic anti-mouse CD4 or anti-mouse CD8 rat mAb in vitro before their injection into the Igha/b newborns or in vivo after their injection into the Igha/b newborns. Exposure to either anti-CD8 or anti-CD4 mAb in vitro or in vivo leads to loss of the capacity of Ts to induce Igh-1b allotypic suppression. Mixing CD4+-cell-depleted Ts and CD8+-cell-depleted Ts preparations restored the capacity of the cells to induce Igh-1b suppression. Thus, both CD4+ CD8- Ts and CD4- CD8+ Ts are required for the induction of this allotypic suppression. Bone marrow cells and B splenocytes from Igh-1b-suppressed adult Igha/b mice were shown to be able to durably express Igh-1b when transferred into irradiated Igha/a BALB/c hosts whereas whole spleen cells from such donors failed to do it. Abrogation of Igh-1b suppression by in vivo anti-CD8 mAb treatment was achieved in adult Igha/b heterozygotes but with a lower efficiency than in adult Ighb/b homozygotes, all being chronically Igh-1b suppressed. The CD4- CD8+ cell population essential for maintaining this suppression is resistant to in vivo 600 rad irradiation and seems to be slightly inhibited by in vivo administration of free Igh-1b.
Regulation of IL-1 and TNF-alpha expression during the differentiation of bone marrow derived macrophage.
Authors: Myers M J , Pullen J K , Ghildyal N , Eustis-Turf E , Schook L B 
Published: December 2022

Abstract
Macrophage differentiation is accompanied by the acquisition of both Ag presentation and tumoricidal activities. In this set of experiments, the expression of IL-1 by bone marrow-derived macrophage (BMDM) was found to be highly regulated, with both the expression of IL-1 mRNA and mIL-1 appearing only at discrete stages of activation. The accumulation of IL-1 alpha (membrane) mRNA was induced by endotoxin but not IFN-gamma or CSF-1. mIL-1 was detected by D10.G4.1 T cells on BMDM only after 7 days of in vitro differentiation. Secreted IL-1 beta was detected by day 3 of culture, with enhanced production observed after activation with endotoxin. IL-1 beta mRNA was found to be constitutively expressed in BMDM as early as day 3 of culture. The expression of IL-1 beta mRNA was up-regulated by endotoxin after 30 min of exposure with maximal expression occurring after 2 to 6 h of exposure. Constitutive expression of IL-1 alpha mRNA was not detected but 1 h of endotoxin exposure resulted in the appearance of IL-1 alpha transcripts. As with IL-1 beta, TNF-alpha mRNA was also constitutively expressed during a wide time period of differentiation; however, in contrast, to IL-1 beta, TNF-alpha mRNA expression was up-regulated by both endotoxin and IFN-gamma. The expression of TNF-alpha macrophage by BMDM coincided with the acquisition of tumoricidal activity. An examination of the mRNA sequences encoding the proto-oncogenes c-myc and c-fms demonstrated the expression of c-myc only on day 3, whereas c-fms was constitutively expressed throughout the culture period. Endotoxin stimulation of BMDM resulted in a transitory increase in c-myc expression only at day 3 of culture, whereas endotoxin had no effect on c-fms expression until 7 days of culture at which time expression declined. In contrast, the expression of transferrin receptor mRNA transcripts, which were also constitutively expressed throughout the entire culture period, were not affected by stimulation with either endotoxin or IFN-gamma. These results indicate BMDM expression of the affector molecules IL-1 alpha and beta and the effector molecule TNF-alpha are regulated separately during unique "differentiation-specific" phases of development.
Role for the third constant domain of the IgG H chain in activation of complement in the presence of C1 inhibitor.
Authors: Okada M , Utsumi S 
Published: December 2022

Abstract
The multidomain architecture of Ig H chains was initially implicated in the variety of functions imposed on each species of Ig. However, the activation of C by IgG is the only function that has been attributed to a single domain of C gamma 2, whereas most of other functions of IgG require both C gamma 2 and C gamma 3 domains. This one domain-one function relationship in the C activation by IgG, too, was questioned recently by the fact that a C gamma 3-less fragment of rabbit IgG, F(acb)2, is definitely less capable of activating C than intact IgG. Here we reexamined capacities of F(acb)2 to bind and activate C1 in the presence and absence of C1 inhibitor (C1-In) in comparison with intact IgG, by using SRBC sensitized with these proteins (EFacb, EIgG). At an ionic strength of 0.065 and 37 degrees C, where C1q was bound equally well by these cells and the dissociation was limited, C1s, presumably in the form of C1r2C1s2, dissociated from EFacb at a rate 7-fold greater than that from EIgG, irrespective of the presence or absence of C1-In. A physiologic concentration of C1-In reduced the rate of C1 activation by EFacb to 5% that by EIgG. The results present evidence that the C gamma 3 domain, too, plays a crucial part in the C1 activation process by stabilizing the zymogenic conformation of C1 and protecting it from the attack by C1 inhibitor.
Purification and analysis of an antigen-specific suppressor factor from a T cell hybridoma specific for phenyltrimethylamino hapten.
Authors: Webb D R , Semenuk G , Krupen K , Jendrisak G S , Bellone C J 
Published: December 2022

Abstract
The synthetic monovalent antigen L-tyrosine-p-azophenyltri-methylammonium (tyr (TMA)) induces in A/J mice, a cascade of regulatory T cells in the absence of any detectable effector function (e.g., CTL, delayed-type hypersensitivity, etc.). An important component of the activated T cells is a first order suppressor T cell or Ts1 that is Ly-1+2-, functions only at the afferent limb of the anti-TMA response, binds the TMA ligand and bears cross-reactive idiotypes associated with anti-TMA antibodies. This Ts1 produces a suppressor factor (TsF1) that binds the TMA ligand, bears the cross-reactive idiotypes and I-J determinants and functions to induce an idiotype-specific Ts2 population. To study the biochemistry of this TsF, use was made of T cell hybridomas that constitutively produce TMA-TsF1 (8A.1 and 8A.3). The TsF1 was purified from culture supernatant or cell extracts by (NH4)2SO4 precipitation, reverse phase HPLC and either affinity chromatography or by preparative IEF. The TsF1 has an isoelectric point of 6.5 and a m.w. of 26,000 or 62,000 as analyzed by SDS-PAGE or high performance molecular sieve chromatography. Its precipitation in 30 to 40% (NH4)2SO4; elution pattern from reverse phase high performance columns; its capacity to bind to a mAb specific for L-glutamic acid 60L-alanine30-L-tyrosine10 (GAT)-TsF1 strongly suggest that this protein belongs to the same family of proteins as do the GAT-TsF1 described previously. Most noteworthy is that although these TsF1 proteins show remarkable similarities, they are absolutely specific in their biologic activity; TMA-TsF1 will not suppress the response to GAT-BA-TNP and GAT-TsF1 will not suppress the response to TMA-BA-TNP. Thus the TMA-TsF1 represents a second example of a unique group of Ag-specific proteins whose function is to induce or activate other suppressor T cells in the primary immune response to Ag.
Alterations in the antigenic structure of two major HSV-1 glycoproteins, gC and gB, influence immune regulation and susceptibility to murine herpes keratitis.
Authors: Hendricks R L , Tao M S , Glorioso J C 
Published: December 2022

Abstract
We previously demonstrated that anterior chamber (AC) injection of HSV-1 before or simultaneous with topical corneal HSV-1 infection resulted in cellular immune tolerance of HSV-1 Ag and a reduced frequency of corneal stromal lesions. In the present study, we have investigated the role of the HSV-1 cell-surface glycoproteins gC and gB in the induction of tolerance, and the resulting reduced susceptibility to HSV-1 corneal stromal disease. These studies utilized mutant strains of HSV-1 with deletion or point mutations in the gene coding for gC or gB. Groups of mice received topical corneal infections with wild-type HSV-1, followed by AC injection of the same eye with wild-type HSV-1 or a mutant strain. Varying the antigenic composition of the virus injected into the AC resulted in three distinct patterns of immune responsiveness. In agreement with our previous findings, AC injection of wild-type HSV-1 induced a state of HSV-1 specific tolerance that extended to both the delayed type hypersensitivity (DTH) and CTL responses. A mutant strain lacking gC (gC-) induced partial tolerance characterized by undetectable CTL activity but a normal DTH response. A mutant strain lacking gB (gB-) caused partial suppression of the CTL response and no reduction of the DTH response. Thus, whereas gB may be involved in CTL tolerance induction in this model, gC clearly is not involved. In contrast, both gC and gB must be present in the AC to induce detectable DTH tolerance. The latter interpretation was strengthened by the observation that AC injection of a mixture of gC- (expressing normal gB) and gB- (expressing normal gC) effectively suppressed the DTH response to wild-type HSV-1. A panel of mar mutants with individual point mutations affecting gC and gB was used to identify the epitopes responsible for induction of DTH tolerance. Two of the gC mutants failed to induce DTH tolerance to wild-type HSV-1 when injected into the AC, suggesting that the sites on the gC molecule that are altered by these mutations are important for the induction of DTH tolerance. Similarly, one of the mar mutants for gB uniformly failed to suppress the DTH response, while another had a variable effect. The unique pattern of cellular immune reactivity exhibited by the mice receiving simultaneous topical corneal infection with wild-type HSV-1 and AC injection of gC- (no CTL but normal DTH) was associated with significantly reduced susceptibility to HSV-1 corneal stromal lesions.(ABSTRACT TRUNCATED AT 400 WORDS)
Idiotype variants emerging after anti-idiotype monoclonal antibody therapy of a murine B cell lymphoma.
Authors: Weiner G J , Kaminski M S 
Published: December 2022

Abstract
One of the difficulties encountered with the treatment of human B cell malignancies with anti-Id antibodies is the emergence of Id variants. The current study was designed to investigate this phenomenon further by using the murine B cell lymphoma model 38C13. Tumors were harvested that developed despite treatment with the anti-Id antibody S1C5 in mice inoculated with 38C13 cells and evaluated by immunofluorescence. Various phenotypes were found among escaping tumor cells. Some cells continued to react with S1C5 whereas others lost S1C5 reactivity. Among these latter cells, some continued to express surface IgM kappa, whereas others no longer expressed surface mu or kappa. After Id variant cell lines were established, immunofluorescence and ELISA of cell lysates from the surface IgM kappa- lines revealed persistent intracellular mu H chain but no detectable kappa. Surface IgM kappa+ lines were fused with myeloma cells and the Ig proteins secreted by the resultant hybridomas analyzed. The apparent m.w. of the mu-chains of these rescued Ig was the same as wild-type 38C13, whereas the kappa-chains were either the same or different in m.w. from the wild type. The IgM kappa of the variant line, T3C, weakly reacted with S1C5 and did not react with other anti-Id antibodies. The IgM kappa of the other variants were nonreactive with all the antibodies. Immunofluorescence of these surface Ig+ variants confirmed this finding. Some of the surface Ig+ and Ig- variant lines grew identically to wild-type tumor in vivo, but only the weakly S1C5-reactive variant T3C was inhibited in its growth by S1C5. Moreover, T3C was the only one of these lines capable of being lysed in vitro with S1C5 by antibody-dependent cellular cytotoxicity. Further studies revealed that surface Ig+ and Ig- variants emerge in escaping tumors with similar frequency and that these variants represent a major mode of tumor escape from anti-Id treatment in this model.
Selective loss of HLA-A or HLA-B antigen expression in colon carcinoma.
Authors: Momburg F , Ziegler A , Harpprecht J , Möller P , Moldenhauer G , Hämmerling G J 
Published: December 2022

Abstract
A panel of colorectal carcinomas has been examined immunohistologically with mAb specific for allodeterminants of HLA-A or HLA-B, and with mAb reactive with HLA-A,B,C framework determinants or beta 2-microglobulin. Out of 85 carcinomas, 5 cases were completely negative for all class I Ag in the tumor cell population. Fifteen cases exhibited a differential expression of HLA-A and HLA-B products in all tumor cells or in a subset. Such tumor cells showed strong staining with monomorphic HLA antibodies but failed to stain with certain allospecific mAb. Negativity of tumor cells was scored only when normal stromal cells within the tumor mass were clearly labeled, indicating expression of the particular allodeterminant(s) in the given tissue. Four carcinomas showed a selective loss of HLA-A2 or a non-A2 HLA-A allospecificity in all tumor cells or a major subset, whereas HLA-B Ag were expressed. Seven cases showed a selective loss of the HLA-Bw6 superspecificity in the tumor cell population; HLA-Bw4 and HLA-A Ag were present. Three cases exhibited a combined loss of HLA-A2 and HLA-Bw6 Ag, with non-A2 HLA-A and HLA-Bw4 Ag being expressed. A further case was HLA-Bw6/Bw4 negative in a major tumor cell subset and HLA-A negative in the complementary minor subset. The results show that a considerable proportion of colorectal carcinomas is heterogeneous with regard to HLA-A and HLA-B expression. The reasons for the appearance of tumor subsets with complete loss of class I Ag or selective loss of only HLA-A or HLA-B Ag are not clear, but it is conceivable that some of them arose because they have escaped immunoselection.
The expression of T cell receptor-associated proteins during T cell ontogeny in man.
Authors: Campana D , Janossy G , Coustan-Smith E , Amlot P L , Tian W T , Ip S , Wong L 
Published: December 2022

Abstract
The expression of TCR-associated molecules was examined in human fetal and postnatal tissues. From gestational wk 7 onward in the fetal liver, putative prothymocytes have been identified with cytoplasmic CD3 positivity (cCD3+). These immature cells are TdT- and do not express membrane CD3 (mCD3-) or TCR beta identified by beta F1, but show CD7 and CD45 positivity without CD1, CD2, CD5, CD4, CD8, CD10, and class II Ag. Their high proliferative activity is indicated by greater than 85% Ki67 positivity. After the 10th wk, beta F1+, mCD3+ cells also appear in the liver and these are mostly Ki67- but no TCR gamma delta-bearing cells can be identified at such an early stage of extrathymic development. In the mCD3- TdT-fetal thymus (10 1/2 to 18th wk) cCD3+, mCD3- CD1-blasts proliferate (Ki67+) and lack TCR-beta or TCR-gamma delta. The TdT-, CD1+ cortical thymocytes develop into TCR-beta + and WT31-positive (TCR-alpha beta +) cells. Subsequently TdT-positive thymocytes become detectable around 19 to 20 wk, and in such glands the peak of proliferative activity is seen among TdT+, cCD3+ cells which appear to acquire, in a regular sequence, cytoplasmic beta F1 (TCR-beta), mCD3, and TCR-alpha beta (WT31 positivity) together with the loss of TdT and Ki67 positivity. A newly described transitional population of cells is TdT-, beta F1+ but exhibits no detectable WT31 positivity. These cells correspond to the CD1+, mCD3+ thymocytes and are probably the targets of thymic selection. The cells of the TCR-gamma delta lineage, detected by mAb TCR-delta-1 and delta TCS1, are rare (0.02 to 0.5%) among thymocytes from gestational wk 10 1/2 onward through the whole span of thymic development, but these cells include a proportion (18 to 59%) of cells expressing CD1 Ag, suggesting that these TCR-gamma delta cells differentiate in the thymus. Among the CD1+, TCR-gamma delta + thymocytes, no TdT positivity can be detected.
Immortalization of EBV-infected B cells is not influenced by exogenous signals acting on B cell proliferation. Effects of mutant EL-4 thymoma cells and transforming growth factor-beta.
Authors: Straub C , Zubler R H 
Published: December 2022

Abstract
We have recently developed a culture system in which 90% of B cells from human peripheral blood or spleen are induced to strongly proliferate and generate short-term clones of a mean of about 400 antibody-secreting cells. B cells are stimulated by mutant EL-4 thymoma cells in conjunction with T cell supernatant. In the present study, we first investigated whether the frequency of B cell immortalization by EBV would be higher in this system than in a conventional system by using PBMC as fillers. The results showed that the EBV-dependent cloning frequency (0.7%) was not increased compared with the system with the use of PBMC (2.1%). However, the short term proliferation of EBV-infected B cells was 20 times increased in the EL-4 system and EBV nuclear Ag-positive cells participated in this response. Recent reports showed that transforming growth factor-beta (TGF-beta) inhibited the growth of normal B cells, whereas the growth of EBV-immortalized (lymphoblastoid) cells was not inhibited. We have studied the effects of this cytokine in the EL-4 system. TGF-beta (200 pg/ml) was found to inhibit the proliferative response of normal B cells by greater than 95% and the short term response of EBV-infected B cells by 78%. In contrast, the EBV-dependent long term cloning frequency, as well as the proportion of clones producing IgM, IgG, or IgA, was not influenced at all by TGF-beta. In conclusion, potent modulation of the early proliferative response of an EBV-infected B cell population by either stimulatory or inhibitory exogenous signals did not influence the number of cells that subsequently became immortalized.
Induction of class II MHC antigen expression in macrophages by Mycoplasma species.
Authors: Stuart P M , Cassell G H , Woodward J G 
Published: December 2022

Abstract
Several different Mycoplasma species have been shown to act as mitogens for either T or B cells and as stimulators of macrophage tumoricidal activity. In this report, we show that at least five different species of Mycoplasma are capable of inducing class II MHC expression on macrophages. We have observed significant induction of class II MHC surface expression on the myelomonocytic cell line, WEHI-3, as early as 24 h after deliberate infection of cultures, reaching maximal levels by 4 days. This induction was also apparent at the mRNA level as assessed by Northern blot analysis by using A alpha, E alpha, and A beta probes. However, unlike many other previously described MHC-inducing agents, mycoplasmas failed to induce class I MHC expression at either the cell surface or mRNA levels. Kinetic analysis revealed that induction of class II mRNA by mycoplasmas was slower than induction by IFN-gamma requiring 24 h rather than 8 h for significant increases to be noted. Induction by mycoplasmas does not require the presence of live organisms and remains active after heat treatment of 90 degrees C for 30 min. We have also demonstrated that mycoplasma infection of primary bone marrow macrophage cultures leads to the induction of both class I and class II genes and, as in the case of WEHI-3, this induction does not require the presence of live organisms. These data indicate that several Mycoplasma species have the capacity to induce class II MHC expression in WEHI-3 and both class I and class II MHC expression in bone marrow macrophage cultures in the absence of any T cell products.
IL-2 secretion is pertussis toxin sensitive in a T lymphocyte hybridoma.
Authors: Stanley J B , Gorczynski R M , Delovitch T L , Mills G B 
Published: December 2022

Abstract
Interaction of specific ligands with TCR initiates a cascade of biochemical events which leads to expression of high affinity IL-2R and subsequent IL-2 secretion. Activation of phospholipase C (PL-C) is considered to be a key event in the initiation of this cascade. However, in addition to this PL-C-dependent pathway, PL-C-independent pathways have been hypothesized. Identification of the steps constituting these PL-C-independent pathways has been difficult because activation of PL-C and the subsequent cascade of events mask the effects of such pathways. Specific inhibitors for PL-C, or mutants defective in, the PL-C pathway would facilitate delineation of alternative activation pathways. We have identified a murine pork insulin/IAd-specific T cell hybridoma, B8P3.11, in which perturbation of the B8P3.11 TCR by either Ag in association with Ia, anti-CD3 antibodies, or a mitogenic lectin does not induce increases in myo-inositol 1,4,5-triphosphate production or cytosolic free calcium, yet it does lead to IL-2 secretion. Treatment of B8P3.11 with pertussis toxin, at concentrations which ADP-ribosylate GTP-binding proteins, inhibits IL-2 secretion. Thus, signal transduction resulting in IL-2 secretion by B8P3.11 likely involves a G protein. In contrast, TCR/ligand interaction activates the PL-C-dependent pathway in LBRM 331A5, a T cell lymphoma. Furthermore, pertussis toxin treatment, which blocks IL-2 secretion by B8P3.11, does not alter IL-2 secretion by LBRM 331A5. However, similar pertussis toxin substrates are present in both cells. Therefore, B8P3.11 T cells should help to elucidate PL-C-independent activation pathways.
A single VH gene is utilized predominantly in anti-BrMRBC hybridomas derived from purified Ly-1 B cells. Definition of the VH11 family.
Authors: Hardy R R , Carmack C E , Shinton S A , Riblet R J , Hayakawa K 
Published: December 2022

Abstract
By establishing hybridomas from two distinct surface IgM+ splenic B cell populations, Ly-1 B cells and "conventional" (Ly-1-) B cells, we found that the Ly-1 B population includes a 30 to 70 times higher frequency (1 to 2%) of cells with specificity for bromelain treated autologous red blood cells (anti-BrMRBC) when compared with conventional B cells (0.03%). We cloned and sequenced the V genes encoding anti-BrMRBC antibody from two hybridomas made with Ly-1 B cells sorted from the spleen of SM/J mice. The VH sequence (for both) is identical with the previously reported sequence associated with this specificity and belongs to a new VH gene family. This gene family, defined here as VH11, has only two members and is the predominant VH rearranged in a collection of Ly-1 B derived anti-BrMRBC hybridomas, always in association with a single VL gene (a member of the V kappa 9 family). Furthermore, analysis of hybridomas made with Ly-1 B cells sorted from the peritoneum reveals a yet higher increased frequency of VH11-encoded anti-BrMRBC specificity (30%). This variation in frequency of anti-BrMRBC in the Ly-1 population depending on location, together with the repeated association of VH11 with a particular V kappa gene suggest that antigen driven selection is (at least in part) responsible for the biased V gene expression seen in this population. Furthermore, a mechanism that might contribute to biased expression, preferential rearrangement due to close proximity to J (as seen in pre-B lines), is excluded by localization of VH11 5' to several of the more J-proximal families (Q52, 7183).