bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequences of the VH and VL regions of murine monoclonal antibodies against 3-fucosyllactosamine.
Authors: Kimura H , Cook R , Meek K , Umeda M , Ball E , Capra J D , Marcus D M 
Published: December 2022

Abstract
Many mAb that bind the carbohydrate antigenic determinant 3-fucosyl-lactosamine (3-FL), Gal beta 1-4[Fuc alpha-3]GlcNAc-R have been raised in BALB/c mice, and we are studying the structure and regulation of these antibodies. In this report, we present the first information about their amino acid sequences and the Ig gene segments used to encode them. V regions of the H and L chains of three anti-3-FL antibodies, PMN6, PMN29, and PM81, were sequenced by a combination of mRNA and amino acid sequencing. The L chain sequences of PMN6 and PM81 antibodies indicate that their VK and JK regions are encoded by VK24B and JK1 germ-line genes, respectively. The nucleotide and amino acid sequences of the H chains suggest that the three anti-3-FL antibodies are encoded by the VH441 gene segment of the X24 VH family, and this conclusion was supported by Southern filter hybridization with VH441 and JH3-JH4 probes. PMN29 has at least 11 amino acid substitutions, which is an unusually large amount of somatic mutation for an IgM antibody. Previous analyses of BALB/c genomic libraries with VHX24 and VH441 probes make it unlikely that this VH family contains additional germ-line genes, but this possibility cannot be excluded. All three antibodies use the DQ52 and JH4 gene segments. The single VH and VL gene segments used to encode the anti-3-FL antibodies is in contrast to the multiple VH and VL segments used by antibodies against other carbohydrate Ag such as alpha 1-6 dextran and group A streptococcal carbohydrate. VH441 also encodes the VH regions of antibodies against galactan and levan (beta 2-6 fructosan). The similarities among VH segments of antibodies against 3-FL, levan, and galactan, and the striking differences in their CDR3 sequences, suggest that CDR3 plays an important role in the formation of the Ag binding site. The use of a single VH segment from the smallest VH gene family by antibodies against at least three different carbohydrate determinants is noteworthy. It raises the possibility that the amino acid sequence encoded by VH441 has some general structural features that make it particularly well adapted for binding to carbohydrate sequences.
Protein Rou. A human IgA hybrid.
Authors: Mihaesco E , Gendron M C , Congy N , Frangione B 
Published: December 2022

Abstract
Protein Rou is a human IgA2 myeloma protein that carries the isoallotype marker n A2m(2). Partial amino acid sequence of its H chain (alpha) shows that the hinge region and the CH2 domain are homologous to alpha 2-chain and the CH1 and the CH3 domains homologous to alpha 1. Moreover, the CH1 domain contains the H-L disulfide bond identical to alpha 1. It is concluded that Rou H chain is a hybrid molecule caused by a recombination between alpha 1 and alpha 2 genes. The recombination event occurred between alpha 1-exon 1 and alpha 2-exon hinge and corresponds to position 222-223 of the alpha-chain.
Cytochalasin stimulates phosphoinositide metabolism in murine B lymphocytes.
Authors: van Haelst C , Rothstein T L 
Published: December 2022

Abstract
The ability of cytochalasin to alter phosphoinositide metabolism was evaluated in naive, murine splenic B lymphocytes. The generation of total inositol phosphates was stimulated by treatment with cytochalasin D, as was the generation of inositol trisphosphate. The cytochalasin-induced increase in inositol phosphates appeared to depend on interaction with actin, and it was inhibited by phorbol esters. Inositol phosphate production was not stimulated in splenic T lymphocytes. The results suggest that the previously observed increase in intracellular calcium produced by cytochalasin is part of a more generalized signaling event that includes phosphoinositide turnover, and, further, raise the possibility of a functional association between actin and phospholipase C.
Cell surface expression and alloantigenic function of a human class I MHC heavy chain gene (HLA-B7) in transgenic mice.
Authors: Chamberlain J W , Nolan J A , Gromkowski S H , Kelley K A , Eisenstadt J M , Herrup K , Janeway C A , Weissman S M 
Published: December 2022

Abstract
We have introduced the gene encoding the heavy chain of the human MHC class I Ag HLA-B7 into transgenic mice. The gene was shown to be expressed at both the RNA and protein level. Cell surface HLA-B7 was detected on whole spleen cells by immunoprecipitation and on purified T cells by flow cytometry (FACS). Normal mice immunized with H-2-syngeneic B7-transgenic spleen cells generated CTL capable of killing transgenic cells and B7-expressing human JY cells. Anti-HLA mAb blocked the killing of JY cells. These results indicate that the human class I Ag HLA-B7 can be expressed at the surface of transgenic spleen cells in the absence of human beta 2-microglobulin, and that a significant fraction exists in a form recognizable by nontransgenic CTL as a major histocompatibility Ag unrestricted by H-2.
CD3/Ti gamma A: a functional gamma-receptor complex expressed on human peripheral lymphocytes.
Authors: Faure F , Jitsukawa S , Triebel F , Hercend T 
Published: December 2022

Abstract
We have recently developed a mAb designated anti-Ti gamma A, which was found to immunoprecipitate from the well characterized CD3+ TCR alpha/beta- F6C7 fetal clone a CD3-associated disulfide-linked gamma-glycoprotein. This antibody recognizes approximately 3% of adult peripheral lymphocytes and delineates a CD2+ CD3+ TCR alpha/beta- CD4- NKH1- subset where expression of CD8 appears to vary widely from one individual to another. In the present study, we have used anti-Ti gamma A mAb to assess whether gamma-chains expressed on these adult lymphocytes are used as functional R. The two activities which have been associated thus far with TCR gamma+ cells, that is, IL-2-dependent proliferation and non-MHC-restricted cytotoxicity, were investigated here by using either resting or activated Ti gamma A+ lymphocytes. On the resting state, these cells (which appear as a very homogeneous population of granular lymphocytes) mediate little if any NK activity that could not be augmented by anti-Ti gamma A mAb. In contrast, after initial stimulation by PHA plus rIL-2 and subsequent culture in the presence of IL-2, activated Ti gamma A+ lymphocytes were strongly lytic against a series of conventional NK target cell lines. This cytotoxic function was either blocked or enhanced by anti-Ti gamma A mAb, depending upon experimental conditions. With respect to proliferation, it was possible to induce responses of resting Ti gamma A+ lymphocytes with antibody-coated CNBr beads only in the presence of exogenous IL-2, whereas, in culture, the same cells proliferated directly and secreted IL-2 after treatment by anti-Ti gamma A beads. Taken together, these data demonstrate that a major subset of circulating CD3+ TCR alpha/beta- lymphocytes use protein products of T cell gamma rearranging genes as functional R structures.
Isotype-specific immunoregulation. Systemic antigen induces splenic T contrasuppressor cells which support IgM and IgG subclass but not IgA responses.
Authors: Kitamura K , Kiyono H , Fujihashi K , Eldrige J H , Beagley K W , McGhee J R 
Published: December 2022

Abstract
In the present study, we have isolated and characterized the Lyt-1+, -2- T contrasuppressor (Tcs) cells from mice systemically primed with SRBC. Adoptive transfer of splenic Tcs cells from these mice abrogates oral tolerance and supports IgM and IgG anti-SRBC plaque-forming cell (PFC) responses; however, unlike the responses seen after transfer of Tcs cells derived from orally primed mice, low IgA responses were seen. Mice systemically primed with lower SRBC doses (0.01 to 1%) exhibited contrasuppression only within the L3T4- T cell subset, whereas mice primed with a high dose of SRBC (10%), harbored Lyt-1+, -2- Tcs cells in both the L3T4+ and L3T4- subsets. Both the L3T4- and L3T4+ Tcs cell subsets supported IgM and IgG responses when adoptively transferred to orally tolerized mice, and when added to tolerized spleen cell cultures. Splenic Tcs cells from systemically primed mice supported mainly IgG1 and IgG2b subclass anti-SRBC PFC responses, a pattern also seen with Tcs cells derived from orally primed mice. Both L3T4+ and L3T4- Tcs cells from systemically primed mice exhibited well established characteristics of contrasuppressor cells including binding to Vicia villosa lectin and expression of I-J. The splenic effector Tcs cells which support IgM, IgG1 and IgG2b anti-SRBC PFC responses are antigen-specific, since both L3T4- and L3T4+ Tcs cells from spleens of mice primed with 10% SRBC reverse tolerance to SRBC, but not to horse erythrocytes (HRBC). Further, both L3T4- and L3T4+ Tcs cells from HRBC-primed mice reverse tolerance to IgM and IgG anti-HRBC, but not to anti-SRBC responses. Isolation of T3-positive Lyt-1+, -2- and L3T4- Tcs cell subsets by flow cytometry followed by adoptive transfer, showed that effector Tcs cells express T3 and presumably contain an Ag-R (TCR-T3 complex). These studies show that systemic priming with heterologous RBC induces splenic Ag specific Tcs cells in a dose-dependent manner, which support IgM and IgG subclass responses, but not IgA responses.
Characterization of antigen processing and presentation by resting B lymphocytes.
Authors: Gosselin E J , Tony H P , Parker D C 
Published: December 2022

Abstract
The production of antibody to a thymus-dependent Ag requires cooperation between the B cell and an Ag-specific Th cell. MHC restriction of this interaction implies that the Th cell recognizes Ag on the B cell surface in the context of MHC molecules and that the Ag-specific B cell gets help by acting as an APC for the Th cell. However, a number of studies have suggested that normal resting B cells are ineffective as APC, implying that the B cell must leave the resting state before it can interact specifically with a Th cell. Other studies, including our own with rabbit globulin-specific mouse T cell lines and hybridomas, show that certain T cell lines can be efficiently stimulated by normal resting B cells. One possible explanation for the above contradiction is that our B cells have become activated before presentation. Here we show that presentation by size-selected small B cells is not the result of nonspecific activation signals generated by the T cells or components of the medium. Also, although LPS activation does increase the efficiency of presentation by small B cells, use of large cells in place of small cells or preincubation of resting B cells with mitogenic doses of anti-Ig does not. Another possibility that we considered was that small B cells are unable to process Ag and that we had selected T cell lines that were capable of recognizing native Ag on the B cell surface. In the majority of cases, experiments with B cell lines and macrophages have shown that Ag presentation requires Ag processing, a sequence of events that includes internalization of Ag into an acid compartment, denaturation or digestion of Ag into fragments, and its return to the cell surface in the context of class II MHC molecules. The experiments reported here show that our T cell lines require an Ag processing step and that small resting B cells, like other APC, process Ag before presenting it to T cells. Specifically, we show that an incubation of 2 to 4 h is required after the Ag pulse before Ag presentation becomes resistant to irradiation. Shortly after the pulse, the Ag enters a pronase-resistant compartment. Although efficient Ag presentation requires initial binding to membrane Ig, Ag is no longer associated with membrane Ig at the time of presentation and is not presented in its intact form, because removal of membrane Ig by goat anti-Ig blocks presentation before but not after the Ag pulse.
Resting B lymphocytes can be triggered directly through the CDw40 (Bp50) antigen. A comparison with IL-4-mediated signaling.
Authors: Gordon J , Millsum M J , Guy G R , Ledbetter J A 
Published: December 2022

Abstract
Resting tonsillar B lymphocytes were shown to enlarge and become more buoyant when exposed to either IL-4 or a mAb (G28-5) to the 50-kDa CDw40 Ag. A striking feature of activation through CDw40 was the promotion of strong homotypic adhesions which did not occur in populations cultured with IL-4. Whereas the CDw40 antibody down-regulated its target Ag, an increased expression of CDw40 accompanied IL-4 stimulation. Similarly, only IL-4, and not the CDw40 antibody, was able to induce the appearance of CD23 on the resting B cell surface. Functionally, the major consequence of ligating CDw40 on resting B cells was that they remained alert to subsequent mitogenic signaling--cells incubated with IL-4 developed the same sluggish response as noted in control cultures. Together, IL-4 and the CDw40 antibody provoked a small, but significant, level of DNA synthesis in tonsillar B cells which was enhanced dramatically by the inclusion of low m.w. B cell growth factor. This latter agent had no discernible direct effect on resting B lymphocytes. The different pathways which have been observed for triggering resting B cells are discussed.
Potentiation of lymphokine-induced macrophage activation by tumor necrosis factor-alpha.
Authors: Heidenreich S , Weyers M , Gong J H , Sprenger H , Nain M , Gemsa D 
Published: December 2022

Abstract
In this study, we examined the possible role of TNF-alpha and lymphotoxin (TNF-beta) as cofactors of macrophage activation. The results demonstrate that both TNF were capable of enhancing the cytostatic and cytolytic activity of murine peritoneal macrophages against Eb lymphoma cells. The potentiation of tumor cytotoxicity became apparent when macrophages from DBA/2 mice were suboptimally activated by either a T cell clone-derived macrophage-activating factor or by IFN-gamma plus LPS. Neither TNF-alpha nor TNF-beta could induce tumor cytotoxicity in IFN-gamma-primed macrophages, indicating that TNF cannot replace LPS as a triggering signal of activation. In LPS-resistant C3H/HeJ macrophages, which were unresponsive to IFN-gamma plus LPS, a supplementation with TNF fully restored activation to tumor cytotoxicity. Furthermore, TNF-alpha potentiated a variety of other functions in low-level activated macrophages such as a lactate production and release of cytotoxic factors. At the same time, TNF-alpha produced a further down-regulation of pinocytosis, tumor cell binding and RNA synthesis observed in activated macrophages. These data demonstrate new activities for both TNF-alpha and TNF-beta as helper factors that facilitate macrophage activation. In particular, the macrophage product TNF-alpha may serve as an autocrine signal to potentiate those macrophage functions that were insufficiently activated by lymphokines.
A 34-amino acid peptide of the third component of complement mediates properdin binding.
Authors: Daoudaki M E , Becherer J D , Lambris J D 
Published: December 2022

Abstract
In this study, a peptide of 34 amino acids from the Mr 40,000 C terminus alpha-chain fragment of C3 was found to mediate properdin (P) binding. Treatment of the Mr 40,000 fragment with CNBr generated one major Mr 17,000 fragment that was capable of binding P. Amino acid sequence data placed the Mr 17,000 fragment within residues 1385 to 1540 of the C3 sequence. After analyzing this sequence for highly conserved segments within the C3 from other species (which bind P) and segments of low similarity within human C4, mouse C5, and alpha 2-macroglobulin (which do not bind P), a 34-amino acid (1402 to 1435) peptide was synthesized. This synthetic peptide bound to P and inhibited its binding to C3b. In addition, it exhibited negative regulatory activity on the alternative pathway as it inhibited the lysis of rabbit erythrocytes by normal human serum. These results show that the P-binding site is located within the residues 1402 to 1435 of the C3 sequence.
Synthesis and release of platelet-activating factor by stimulated human mononuclear phagocytes.
Authors: Elstad M R , Prescott S M , McIntyre T M , Zimmerman G A 
Published: December 2022

Abstract
Platelet-activating factor (PAF) is a potent phospholipid mediator that may participate in inflammatory responses by virtue of its ability to activate platelets, leukocytes, and vascular cells. We examined the synthesis and release of PAF by human peripheral blood monocytes (PBM) isolated by countercurrent elutriation. PAF was produced after stimulation by calcium ionophore A23187 (IoA), opsonized zymosan (OpsZ), and PMA with a relative order of potency IoA much greater than OpsZ greater than PMA. The portion of PAF subsequently released from the cell was dependent on the specific agonist, the time of incubation, and the presence of albumin. Under optimal conditions, PBM released 67, 49 and 32% of the total PAF produced in response to IoA, OpsZ, and PMA, respectively. Changes in PAF metabolism were observed in PBM that were examined after short term adherence or differentiation into macrophages. Adherent PBM accumulated and released less PAF than suspended monocytes, and monocyte-derived macrophages produced less PAF than the parent PBM. The ability of monocytes to release significant amounts of newly synthesized PAF from the cell is unusual among human cell types, which in general retain the vast majority of the lipid, and may be of particular pathophysiologic importance.
Graft-versus-host reaction-induced immune modulation. I. Donor-recipient genetic disparity and the differential expression of Lyt-2, L3T4, and Ly-6 during acute reactions in the host thymus.
Authors: Levy R B , Cotterell A H , Jones M , Malek T R 
Published: December 2022

Abstract
To investigate the effects of graft-vs-host reactions (GvHR) on cells in a central lymphoid compartment, GvHR were induced across class I/II or class II only major histocompatibility complex differences utilizing the parent into nonirradiated F1 hybrid (P----F1) model. Thymocytes were subsequently examined during the acute stage of GvHR for the expression of Lyt-2, L3T4, and Ly-6 cell surface molecules. Class I/II "suppressive" GvHR resulted in a dramatic decrease (greater than 85%) in total thymocyte numbers by 2 wk after parental cell injection. Although a dramatic decrease in the percentages of Lyt-2 (85%----30%) and L3T4 (95%----50%) expression was observed, the percentage of thymocytes expressing Ly-6 was markedly increased compared to uninjected controls (5%----greater than 80%). This increased percentage was not due solely to a selective loss of Ly-6 negative cells from the thymus, since the actual number of Ly-6 positive cells was greater in GvHR mice than in controls. Class II GvHR during the same time interval resulted in a less dramatic decrease (20 to 60%) in total thymocyte numbers. In addition, the effect on the percentages of Lyt-2 (85%----approximately 70%) and L3T4 (95%----approximately 85) expression was subtle and transient. However, intrathymic Ly-6 expression was again clearly enhanced (5%----20 to 30%). Class I/II "proliferative" or "stimulatory" GvHR differ from "suppressive" reactions in that they are characterized by stimulatory pathologic symptoms and the appearance of autoimmune abnormalities. Such GvHR were found to result in minimal alteration of total thymocyte numbers. Similarly, the percentage expression of Lyt-2 and L3T4 was marginally affected. However, the percentage of Ly-6 expression was increased from 5%----20 to 30% and thus these intrathymic lymphocyte profiles more closely resemble those of class II as compared to class I/II "suppressive" GvHR. The present findings therefore demonstrate that major histocompatibility complex differences alone do not necessarily determine the effects of GvHR on recipient thymocytes and that Ly-6 is a useful marker for the early detection of GvHR-associated immunologic events.
Differential regulatory signals delivered by antibody binding to the CD28 (Tp44) molecule during the activation of human T lymphocytes.
Authors: Damle N K , Doyle L V , Grosmaire L S , Ledbetter J A 
Published: December 2022

Abstract
Molecule CD28 (Tp44) is expressed on the surface of majority of human T cells and has been implicated to play an active role in the regulation of T cell growth. The present study examines the effect of antibody binding to the CD28 molecule during T cell activation. Anti-CD28 but not isotype-matched anti-CD5 mAb consistently augmented anti-CD3-induced and IL-2-induced T cell proliferation and subsequent release of soluble CD25 molecule. When added together, mAb anti-CD28 and anti-CD5 acted synergistically to cause 2- to 7-fold enhancement of T cell activation induced by anti-CD3 mAb or IL-2 with no effect on the development of non-MHC-restricted IL-2-activated killer T cells. In contrast, alloantigen-induced T cell proliferation, soluble CD25 release, and the subsequent development of CTL were all inhibited by anti-CD28 mAb. Moreover, alloantigen-induced proliferative response of both CD4+ and CD8+ T cells was inhibited by anti-CD28 without affecting the cytolytic effect of CTL. Because valency of anti-CD28 binding has been implicated as an important factor in signal transduction, this was explored in the allogeneic MLR by using Fab and F(ab')2 fragments of anti-CD28 mAb and anti-mouse kappa mAb. The inhibitory effect of anti-CD28 mAb in the MLR was reversed by cross-linking of anti-CD28 mAb with anti-mouse kappa mAb. In addition, cross-linking of the CD28 molecule on alloactivated T lymphoblasts but not that on resting T cells with anti-CD28 and anti-mouse kappa induced their proliferation in the absence of the priming alloantigen. These results indicate that stimulatory or inhibitory signals delivered through the CD28 molecule are determined by the degree of cross-linking of this molecule. In addition, these results also suggest that Ag-induced CD3-TCR-mediated T cell responses are more dependent on signals delivered through the CD28 molecule than those induced with anti-CD3, and thus these results have implications for potential use of anti-CD28 in sustained propagation of Ag-specific T cells.
Role of the CD22 human B cell antigen in B cell triggering by anti-immunoglobulin.
Authors: Pezzutto A , Rabinovitch P S , Dörken B , Moldenhauer G , Clark E A 
Published: December 2022

Abstract
As B cells mature during ontogeny the CD22 human differentiation Ag is exported from the cytoplasm onto the membrane. Surface expression is lost in terminal differentiation and after activation. In tonsils, CD22 is expressed on the surface of 60 to 80% of the dense B cells. Some IgM+ dense cells, however, and buoyant in vivo activated B cells are CD22-. This differential expression of CD22 and the finding that an anti-CD22 mAb augmented anti-Ig induced B cell proliferation suggested that CD22 may play a role in B cell activation. In this study we have found that CD22+ but not CD22- B cells could be triggered by anti-IgM or anti-IgD to have increased free intracellular calcium ([Ca2+]i). The presence of CD22 rather than of IgD seems to determine the ability of B cells to respond to anti-Ig with a [Ca2+]i flux. Also the proliferative response to anti-Ig or anti-Ig + B cell growth factor was restricted to the CD22+ population. Anti-CD22 mAb, although not inducing [Ca2+]i on their own after binding to B cells, did augment [Ca2+]i fluxes by anti-Ig when cross-linked. Together these results suggest that CD22 may regulate triggering of B cells through surface Ig perhaps by acting as a "bridge" to transmit an early signal into the cytoplasm.