Search PubMed⌕ Search

Biomedical subjects

S K Pierce

Publications and source records attributed to S K Pierce.

At least 109 records · Page 6Linked to original sources
PubMed1984

Synergistic effects of antigen and soluble T-cell factors in B-lymphocyte activation.

Supernatants from phorbol 12-myristate 13-acetate-activated cultures of the mouse EL4 thymoma, or of several mouse T-cell hybridomas stimulated either by their specific antigen or by concanavalin A, induced primary splenic B cells to proliferate and differentiate to antibody-secreting cells. This effect was not due to interleukin 2 and did not require the presence of macrophages. The antibody response was polyclonal, including antibodies specific for 2,4-dinitrophenyl and pigeon cytochrome c, present in amounts of 1% or less of the total immunoglobulin produced. The addition of either of these antigens increased the amount of the corresponding specific antibody. At very high concentrations of dinitrophenyl-hemocyanin the specific response could be depressed. These observations were taken to demonstrate that soluble T-cell factors are sufficient to activate a portion of naive B cells to antibody secretion and that under these conditions in vitro the presence of antigen merely enhances the specific response.

2,4-Dinitrophenol↗
PubMed1983

Primary amines inhibit the triggering of B lymphocytes to antibody synthesis.

Transglutaminase enzyme activity was demonstrated in murine splenic B lymphocytes. Preincubation of cell cultures with primary amines that are known substrates for transglutaminase inhibited the triggering of murine B lymphocytes to form clones of antibody-producing plasma cells. B cells could be rescued from this inhibition by incubating cultures with anti-immunoglobulin or multivalent antigens under nonstimulatory conditions. Rescue of B cells exhibited the same requirements as stimulation, which suggests that rescue is a dynamic process and not simply a receptor-ligand binding event. Primary amines appeared to inhibit an early, T cell-independent event in the B cell activation pathway, which was not sufficient to trigger B cells to form antibody-producing clones. Subsequent receptor-mediated events, required to further trigger B cells, were not inhibited by the presence of primary amines.

Acyltransferases↗
PubMed1982

The collaborative phenotype of secondary B cells is determined by T lymphocytes during in vivo immunization.

Previous studies have demonstrated that the B cells in immune and nonimmune mice manifest different major histocompatibility complex (MHC) collaborative phenotypes with antigen-specific T cells. Immune, or secondary B cells require syngeneic-like MHC recognition by collaborating T cells, and in its absence fail to be stimulated. Primary B cells manifest a much less stringent requisite for MHC recognition by T cells, and under conditions in which secondary B cells fail to be stimulated, primary B cells are stimulated to secrete IgM antibody. Experiments were conducted to determine whether the acquisition of the secondary B cells' MHC collaborative phenotype was dependent on the presence of T cells during in vivo immunization. B cell populations from T dependently and T independently immunized conventional BALB/c and athymic BALB/c nu/nu mice were compared in their ability to collaborate with allogeneic T cells. Although antigen alone promotes the differentiation of several secondary B cell characteristics, including an increase in the frequency of antigen-specific B cells and a preference for IgG1 antibody synthesis in vitro, the acquisition of the secondary B cells' MHC collaborative phenotype was dependent on the presence of T cells during in vivo immunization. B cell populations from T dependently and T independently immunized conventional BALB/c and athymic BALB/c nu/nu mice were compared in their ability to collaborate with allogeneic T cells. Although antigen alone promotes the differentiation of several secondary B cell characteristics, including an increase in the frequency of antigen-specific B cells and a preference of IgG1 antibody synthesis in vitro, the acquisition of the secondary B cells' MHC collaborative phenotype was found to be dependent on the presence of T cells during in vivo immunization. Thus, the restriction imposed on T cell-B-cell-collaborative interactions in secondary humoral immune responses appears to be the result of T dependent antigen-driven events.

Animals↗
PubMed1982

The induction of B cells refractory to antibody-specific immunoregulation.

Subsequent to primary immunization with a hapten-carrier conjugate, and concomitant with an initial antibody response to that antigen, a regulatory mechanism is induced that specifically limits the stimulation of hapten-specific primary B cell responses through the recognition of B cell antibody. Nonimmune B cells are sensitive to this regulation, while secondary B cells are refractory to its suppressive effects. Experiments were conducted to determine the conditions under which refractory B cell populations are generated. B cells from BALB/c and athymic BALB/c nu/nu mice were examined following immunization with the T-dependent antigen dinitrophenylated (DNP) hemocyanin and the T-independent antigen DNP-Ficoll to assess the T cell dependence of the generation of refractory B cells. Evidence is presented that this process is not dependent on the presence or participation of T cells during in vivo immunization, since both T-dependent and T-independent antigens have the potential to induce a refractory B cell population. However, under certain circumstances, T cells can regulate the induction of refractory B cells during in vivo immunization. In addition, it was determined that the immunoregulatory phenomenon can be induced following immunization with both T-dependent and T-independent antigens.

Animals↗
PubMed1982

Antibody-specific immunoregulation is restricted by the major histocompatibility gene complex.

Experiments were carried out to examine the major histocompatibility complex (MHC) restriction of an antibody-specific immunoregulatory function that develops following conventional immunization with hapten-carrier conjugates. It was found that carrier-primed hosts reconstituted with Ly-2.2+ T cells from hapten-carrier-immunized donors were able to suppress adoptively transferred primary B cells. The effective suppression of primary B cell responses was dependent on syngeny between the suppressing T cell population and the target B cells at both MHC and Igh. These findings indicate that T cells that function through the recognition of B cell antibody are restricted in their function by gene products of the MHC, similar to the restrictions observed for the recognition of conventional antigens.

Animals↗
PubMed1981

Balb/c T cells have the potential to recognize the TEPC 15 prototype antibody and its somatic variants.

Immunization of BALB/c mice with phosphorylcholine-Limulus polyphemus hemocyanin (PC-Hy) induces a population of T cells that recognize the predominant PC-binding antibody, TEPC15 (T15). The splenic fragment culture system was used to examine the specificity of these T cells for a series of PC-binding myeloma and hybridoma antibodies representing the prototype variable region of the heavy chain (VH)T 15 sequence as well as somatic variants of the T15 germ line-encoded sequence. Included in this group of PC-binding proteins were both T15-positive and T15-negative antibodies, as defined by anti-idiotypic antibody. T cell help was identified by the ability to promote TNP-specific B cell responses to trinitrophenylated PC-binding proteins. It was found that T cells generated by immunization with PC-Hy recognize both antibodies with the T15 prototype sequence and the putative somatic variants of this sequence. A population of these T cells appear to recognize common determinants shared by these proteins because immunization with T15 itself also induces the recognition of the somatic variants. This suggests that idiotopes encoded in the T15 germ line gene expressed by the T15 prototype idiotype and the somatic variants can function as targets for T cell recognition and are thus regulatory idiotopes.

Amino Acid Sequence↗
PubMed1981

Multiple B cell stimulation by individual antigen-specific T lymphocytes.

Recently, an experimental system has been described which allows for the isolation and antigenic stimulation of individual antigen-specific helper T lymphocytes in collaboration with a nonlimiting number of primary B lymphocytes. In the studies presented in this report, this system has been employed to determine whether an individual T lymphocyte has the potential to interact with more than a single B lymphocyte, when the B cells are of different antigenic specificities. The results of these studies indicate that an individual influenza virus PR 8-specific T lymphocyte has the ability to promote antibody responses of both trinitrophenyl (TNP)- and PR8-specific B lymphocytes in response to the in vitro antigen TNP-PR8. Similar results were obtained when T cells specific for the hapten TNP were used in collaboration with TNP- and PR8-specific B cells. These results demonstrate that an individual T lymphocyte has the potential to collaborate with more than one B lymphocyte, and that these B cells may differ in their antibody receptor for antigen. These results do not rule out a role for idiotype or allotype-specific T cells in antibody responses but, rather, strongly argue that antigen-specific T cells are able to independently initiate primary B cell responses of B cells with distinct antibody receptors. In addition, under these conditions, hapten-specific helper T cells can be readily demonstrated and may facilitate the response of B cells specific for the same or different determinants.

Animals↗
PubMed1981

The functional helper T cell repertoire specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

Experiments have been carried out to examine the potential helper T cell repertoire specific for the random terpolymer GAT on responder, nonresponder, and (responder x nonresponder)F1 murine strains. The ability of GAT-MBSA immunized T cells to collaborate with DNP-specific primary and secondary B lymphocytes of each strain in response to the antigen DNP-GAT was tested with the splenic fragment culture system. The results of these experiments show that there are GAT-specific T lymphocytes in the responder, nonresponder, and F1 strains but that these 3 GAT-specific T cell populations differ in their collaborative potential. In sum, these findings present new evidence that the nonresponder status to the terpolymer GAT is due, in part, to a functional deletion of helper T cells capable of recognizing the antigen in the context of the nonresponder haplotype. Further, a new responsive phenotype is evidenced when F1 secondary B cells are stimulated in nonresponder GAT-MBSA-primed recipients. In this case, rather than the IgG1 responses observed in such strain combinations to other antigens such as DNP-Hy or DNP-Gl phi 9, only IgM responses were obtained. This new phenotype may be the result of GAT-specific suppression of isotype switching by B cells bearing the nonresponder cell surface alloantigens.

Animals↗
PubMed1980

Role of the major histocompatibility gene products in regulating the antibody response to dinitrophenylated poly(L-Glu55,L-Ala35,L-Phe9)n.

These studies were carried out to investigate the potential helper T cell repertoire specific for the random copolymer poly(L-Glu55,L-Ala35, L-Phe9)n(GL phi 9) of responder, nonresponder, and (responder x nonresponder)F1 murine strains. We tested the ability of these T cells to collaborate with dinitrophenyl (DNP)-specific primary and secondary B lymphocytes of each strain in response to the antigen CNP-GL phi 9 in the splenic-fragment culture system. The results of these experiments show that there are GL phi 9-specific T lymphocytes in the responder, nonresponder, and F1 strains; but that these three GL phi 9-specific T cell populations differ in their collaborative potential. Responder T cells are able to collaborate with their own syngeneic responder B cells as well as the allogeneic nonresponder B cells in a syngeneic fashion. The F1 T cell population resembles that of the nonresponder in its ability to collaborate with only responder B cells in a syngeneic fashion. Analysis carried out using appropriately selected mouse strains indicate that these results are unlikely to be a result of positive or negative allogeneic effects. The results obtained suggest that individuals within a given murine strain do possess the capacity to collaborate in a syngeneic fashion with B cells of any other MHC-allogeneic strain as well as their own MHC-identical B cells. The nonresponder status in the response to GL phi 9 appears to be the result of a deletion of T cells capable of recognizing antigen in the context of B cells of the nonresponder haplotype. Thus, the MHC gene products appear to play a determinative role in shaping the expressed helper T cell specificity repertoire within an individual mouse strain.

Animals↗
PubMed1978

Individual antigen-specific T lymphocytes: helper function in enabling the expression of multiple antibody isotypes.

In recent years antigen-specific T cells have been shown to be capable of mediating a number of diverse functions in collaboration with B cells in humoral immune responses. One of the more intriguing roles attributed to helper T cells is the promotion of the synthesis of multiple immunoglobulin isotypes by B cells in T-dependent antibody responses. The experiments presented in this report were carried out to determine if an individual antigen-specific T lymphocyte has the capability to enable the production of antibodies of multiple immunoglobulin heavy chain isotypes. We describe an experimental system which allows for the isolation and antigenic stimulation of individual helper T cells in a splenic environment which provides an excess of primary B cells for collaboration with isolated T lymphocytes. Employing this system we have demonstrated that an individual antigen-specific T lymphocyte, specific for the PR8 strain of influenza virus, has the capacity to enable primary B-cell PR8-specific antibody responses of more than a single immunoglobulin isotype. The implications made by these studies regarding the problem of genetic restrictions regulating T-cell-B-cell interaction is discussed.

Antibody Formation↗
PubMed1978

Acetylcholinesterase: a useful marker for the isolation of sarcolemma from the bivalve (Modiolus demissus demissus) myocardium.

The presence of cholinesterase activity in M. demissus hearts was demonstrated by light- and electron-microscopic histochemistry and by enzymic assay. The enzyme proved to be acetylcholinesterase (AChE) since acetylthiocholine was the preferred substrate, and eserine or BW284C5I inhibited the enzyme activity, while isoOMPA was without effect. The AChE was localized and uniformly distributed along the cell surface membranes of the cardiac muscle cells. A fraction 8-fold enriched in AChE was isolated from pooled ventricles by a combination of differential and sucrose density gradient centrifugation. This sarcolemmal fraction contained little mitochondrial contamination as determined by electron microscopy and by succinate cytochrome c reductase activity. In addition, this fraction stained uniformly for AChE, indicating that it was free of other membrane types (for example sarcoplasmic reticulum which did not stain for AChE). Therefore, this fraction contained purified cell surface membrane free of contamination by other membranous organelles.

Animals↗
PubMed1977

Antibody-specific immunoregulation.

In recent years, much evidence has accumulated which demonstrates that an animal's immune system has the capacity to recognize its own antibody idiotypes. These findings suggest that self-idiotypic recognition may potentially play a role in the regulation of B-cell responses. The experiments presented in this report were carried out to determine if an animal develops the ability to specifically regulate the synthesis of antibodies specific for an antigen, subsequent to primary immunization to the particular antigen and concomitant with an initial antibody response. Employing the splenic fragment culture system we have compared the response of primary donor B cells in irradiated recipients which have been previously immunized to hemocyanin (Hy) alone or dinitrophenyl (DNP)-Hy plus Hy. The results indicated that only 25-30 percent of DNP- specific B cells stimulated by DNP-Hy in Hy immunized recipients could bestimulated by DNP-Hy in recipients immunized with Hy as well as DNP-Hy. B-cell responses to other haptens, such as fluoresceinated-Hy, and secondary DNP-specific B-cell responses were unaffected in DNP-Hy immunized animals. The nontrivial and specific nature of the observed decrease in primary DNP-specific B-cell responses was verified by the finding that the response of CB20 donor cells, which differ from BALB/c mice only in the immunoglobulin heavy chain allotype-linked locus, was unaffected in BALB/c recipient mice which had been immunized with DNP-Hy. Thus, it appeared that during a primary humoral immune response to a T- dependent antigen, an antibody-specific regulatory mechanism is induced which specifically limits the stimulation of hapten-specific primary, but not secondary, B cells. The important implications that these findings have for the understanding of the control of primary B-cell responses and the generation of secondary B cells is discussed.

Animals↗
PubMed1977

Glutamate dehydrogenases from tissues of the ribbed mussel Modiolus demissus: ADP activation and possible physiological significance.

Glutamate dehydrogenase (E.C. 14.1.3) was localized in the mitochondria from heart, gill, mantle and hepatopancreas of this euryhaline bivalve mollusc. Activity levels were low (0.1-0.4 mumoles/min/g wet weight) in all tissues when assayed in the glutamate forming direction. Partially purified gill mitochondrial GDH was most active at pH 8.5. The rate in the glutamate deaminating direction was 10-20% of the rate in the glutamate forming direction. ADP at apparent Ka concentrations of micrometer (glutamate formation) and 170 micrometer (glutamate deamination) enhanced GDH activity, 8- and 4-fold respectively. GDH, in vivo, is probably in the activated form and appears to function in glutamate synthesis rather than ammonia formation. However, based on the low activities obtained, the role of GDH in salinity induced amino acid synthesis seems minimal.

Adenosine Diphosphate↗
PubMed1977

Computer-assisted method for multi-exponential curve fitting for determining cerebral blood flow.

A computer program has been developed for use in determining cerebral blood flow using an inert radioactive gas. The basic algorithm involves the determination of multiple exponential coefficients from the complex concentration-time function. The exponential coefficients are determined by 'peeling' away slower exponentials complex function one at a time. The procedure involves the use of a small laboratory computer in the interactive graphics mode. The method is currently in use analyzing data in a cerebral vascular research laboratory.

Animals↗
PubMed1977

A sampling technique for organic components in human breath.

An analytical sampling system was developed for trace organic components in breath. The sampling system was designed to maximize analyte concentrations while minimizing interference from exogenous contamination. Details of the sampling system design and its operation are presented.

Breath Tests↗
PubMed1977

Role of endogenous murine leukemia virus in immunologically triggered lymphoreticular tumors. I. Development and use of oncogenic cellfree preparations serially passaged in vivo.

Cellfree extracts (CFEs) prepared from (BALB/cJ X A/J)F1 (CAF1) and (BALB/cJ X C57BL/6J)F1 (CB6F1) mice in which a graft-versus-host reaction (GVHR) has been induced are known to be oncogenic, but only after a protracted latent period (mean, 16 mo). Serial passage of such CFEs in successive generations of syngeneic mice inoculated at birth led to the development of two separate oncogenic preparations, the CA serioes in CAF, mice and the CB series in CB6F, mice, in which the mean latent period was reduced to 6 and 12 months, respectively. Both oncogenic preparations contained infectious B-tropic murine leukemia virus (MuLV) and particles with the ultrastructural characteristics of MuLV. No other kind of virus particle was seen. When these preparations were injected into infant syngeneic mice, B-tropic MuLV could be detected in the reticular tissues as early as 2 weeks thereafter. The virus persisted in the reticular tissues and was present in the lymphoreticular tumors that subsequently developed. However, if the same preparation was injected into young adult recipients, there may have been transient MuLV replication, but the virus subsequently disappeared from the reticular tissues and no lymphoreticular tumors developed. Previous experiments showed that MuLV was present in CFEs prepared from CAF, animals with the GVHR but absent in those of normal control mice. Since the lymphoreticular tumors arising in mice with the GVHR were the same as those induced by the CA and CB MuLV preparations, it was concluded that tumorigenesis in mice with the GVHR was caused by endogenous B-tropic MuLV activated by the immunologic disturbance.

Animals↗