A possible relationship between delayed hypersensitivity and cell-mediated immunity.
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Animals↗
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Results for “Epitopes, B-Lymphocyte”
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Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level.
Immune responsiveness to phosphorylcholine (PC) in BALB/c mice has been characterized by combining (a) usuage of highly sensitive radioimmunoassays for quantitation of antibody, heavy-chain class, and idiotype on a weight basis; (b) isolation of PC-specific B cells in fragment cultures; and (c) stimulation in a carrier-primed environment with the PC hapten coupled to carrier through a tripeptide spacer in order to maximize carrier recognition. The specificity and accuracy of the radioimmunoassays have veen verified by specific inhibition, lack of nonspecific binding, and excellent concordance of values for monoclonal antibody concentration obtained independently for Fab and idiotype content. The latter evidence also serves as strong confirmation of the monoclonality of in vitro monofocal responses as well as the preservation of the idiotype on antibodies of differing immunoglobulin classes. The results indicate that while B cells expressing the TEPC 15 idiotype predominate, other idiotypes may be represented by 2-50% of PC-specific precursors, and monoclonal antibodies even of the TEPC 15 idiotype are produced in both the IgM and IgG1 immunoglobulin classes. These findings are confirmed by the analysis of serum antibodies produced in carrier-primed mice immunized with hapten coupled through a tripeptide spacer, thus re-emphasizint the enhancement of primary responsiveness, particularly IgG1 production, by maximizing carrier recognition. The finding of idiotype diversity in the PC response, as well as diversity of expression in terms of quantity and immunoglobulin class of antibody synthesized by the clonal progeny of B cells within the TEPC 15 clonotype, emphasize the heterogeneity of the B-cell population both in terms of specificity repertoire and the physiological state of cells even within a single clonotype.
Animals↗
Antigenic surface determinants of chicken lymphoid cells. II. Selective in vivo and in vitro activity of anti-bursa and anti-thymus sera.
Appropriately absorbed turkey antisera to antigenic surface determinants of chicken bursa (ABS) or thymus cells (ATS) were assessed for their selective immunosuppressive activy in vitro and in vivo. The intraperitoneal injection of ABS or ATS into 2-3-week-old normal white Leghorn chickens entailed a significant depletion of B or T cells respectively from spleen and peripheral blood, while bursa and thymus themselves remained unaffected. The potential of this 'peripheral serological bursectomy and thymectomy' paralleled that found after the conventional surgical procedures with subsequent sublethal irradiation. The mean survival time of skin allografts from donors of genotype B4B4 onto B8B8 recipients was significantly prolonged by treatment with ATS (29 plus or minus 12 days) as compared to untreated (14 plus or minus 2 days), normal turkey serum (12 plus or minus 3 days) or ABS-injected (13 plus or minus 2 days) groups. This selective suppression of a T cell-dependent immune reaction by ATS was also confirmed in vitro by its inhibitory action on the graft-versus-host reactivity of adult peripheral blood lymphocytes in the chorioallantoic membrane assay, where normal turkey serum and ABS were again ineffective. Thus, ABS or ATS produced in avian species may serve not only to delineate B and T cells in vitro, but can also be used for selective manipulation of immune reactions of the chicken in vivo.
Animals↗
The H-2 major histocompatibility complex and the I immune response region: genetic variation, function, and organization.
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Alleles↗
Sequential expression of germ line genes in development of immunoglobulin class diversity.
Differentiation of B cells occurs in two discontinuous stages. Primary differentiation of stem cells to B lymphocytes in birds occurs exclusively in the lymphoepithelial bursa of Fabricius; the fetal liver may serve this function in mammals. In chickens both the size of the B-lymphocyte pool and the generation of precursors for cells secreting different immunoglobulin classes is controlled by the bursa. The latter process involves the sequential expression of genes coding for heavy chain constant regions in the order mu, gamma, alpha. The second stage of B-cell differentiation is antigen-driven, and involves proliferation and maturation of B lymphocytes to plasma cells. Ontogenetic development of different classes of B lymphocytes in mammals is orderly, independent of exogenous antigens, and occurs in the sequence mu, gamma, alpha. A developmental switch in expression of Ch genes, beginning with mu, has been experimentally verified. We favor the hypothesis that generation of class diversity of B lymphocytes occurs during the antigen-independent first stage of differentiation, and that the genetic switch in Ch gene expression follows the sequence mu leads to gamma leads to alpha, but evidence of these points remains inconclusive.
Animals↗
Defense mechanisms against infectious diseases: general considerations with particular reference to morphological and cellular aspects.
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Antibody Formation↗
Epstein-Barr virus-induced transformation of human leukocytes after cell fractionation.
The efficiency of transformation of human lymphocytes after infection with Epstein-Barr virus (EBV) was determined in fractionated and non-fractionated preparations derived from 16 human cord blood samples and two blood samples from adult donors. The transformation efficiency of macrophage-depleted leukocytes was consistently lower as compared to non-fractionated leukocytes. Additional depletion of B-cells resulted in a further decrease. Reduction of T-cells, however, did not influence significantly the transformation rate. In non-fractionated leukocyte cultures, as well as in macrophage-depleted and B-cell enriched cultures, colonies of transformed cells were regularly observed within the first week of cultivation. All cell lines established after EBV-infection revealed membrane-bound immunoglobulin. Reconstruction of macrophages-depleted, B-cell enriched or B-cell depleted cultures with autologous macrophages resulted in an increase of the transfromation efficiency up to the values of non-fractionated leukocyte preparations. Addition of heterologous human embryonic lung fibroblasts resulted in a similar increase. The results support the interpretation that EBV transforms only those cells of the hematopoetic system which are derived from the bone-marrow entity. The transformation efficiency is considerably increased by co-cultivation of lymphocytes with macrophages and heterologous human fibroblasts which seem to excert a feeder-layer effect by enhancing survival of lymphocytes in vitro.
B-Lymphocytes↗
Significance of cellular interactions in the immune response.
Recent investigations relevant to T and B cell cooperation in humoral immunity are discussed from the following aspects: requirement for T cells in antibody responses; T cell facilitation of B cell responsiveness; T cell suppression of B cell responsiveness; evidence for a nonspecific influence of T cells on B cell responsiveness; relevance to clinical disorders.
Animals↗
Relationship between Fc receptors, antigen-binding sites on T and B cells, and H-2 complex-associated determinants.
The relationship between H-2 complex-associated determinants, Fc receptors, and specific antigen-recognition sites on T and B cells was examined by binding and functional assays. The Fc receptor was detected by radiolabeled immune complexes or aggregated human IgG. Both these reagents selectively bound to B cells, not to T cells. When spleen cells, from mice primed to several antigens, were exposed to highly substituted radioactive aggregates, their capacity to transfer both a direct and indirect plaque-forming cell response to these antigens was abrogated. Addition of B cells, but not of T cells, restored responsiveness. Complexed Ig binding to Fc receptors was prevented by pretreatment of mixed lymphoid cell populations with antisera directed against membrane components on the same cell (e.g., H-2) and on other cells (e.g., theta). The lack of specificity of inhibition was thought to be due to the formation on cell surfaces of antigen-antibody complexes which would then attach to the Fc receptor during the incubation precedure. Specific blockade of the Fc receptor during the incubation procedure. Specific blockade of the Fc receptor however occurred when B cells were pretreated with the Fab fragments of anti-H-2 antibody. This was demonstrated autoradiographically and by inhibition of aggregate-induced suicide. The blocking activity of ante-H-2 Fab was removed by absorption with spleen cells from thymectomized irradiated mice but not with thymus cells of appropriate specificity. This suggested that the antibodies involved had specificity for determinants on the B-cell membrane distinct from those coded by the K or D end of the H-2 complex, and either absent from, or poorly represented on, thymus cells. Specific antigen-induced suicide of B cells was achieved simply by incubating the cells with radioactive antigen in the cold. T-cell suicide on the other hand required that the 125I-labeled antigen be presented to the T cells at 37 degrees-C on the surface of spleen cells from antigen-primed mice. Pretreatment of T cells with the Fab fragment of anti-H-2 antibody protected them from the suicide effect. By contrast no such protection of B cells could be achieved by this procedure. In other words H-2 (? Ir)-associated determinants may not only be in close proximity to the antigen-binding site on T cells but, in addition, may be involved in the effective operation of the receptor.
Animals↗
Effects of aging on the differentiation and proliferation potentials of cells of the immune system.
An attempt has been made here to show that the immune system can begin to decline in function shortly after an individual reaches maturity. The decline is due in part to changes in the environment of the cells but primarily to changes in the precursor cells of the system. This is reflected in their inability to proliferate and possibly differentiate efficiently. These findings show that the immune system can serve as an excellent model to study how aging can perturb the process of cells undergoing proliferation and differentiation.
Aging↗
Cellular basis of the immune response.
Lymphocytes, the cells competent to initiate immune responses, can be divided into two major groups: thymus-derived or T cells responsible for "cellular immunity" (e.g. delayed hypersensitivity reactions) and bursa (or bursa-equivalent) derived or B cells which produce immunoglobulin (antibody) molecules and are involved in "humoral immunity". "Accessory" cells, such as monocytes (or macrophages), polymorphonuclear leucocytes and mast cells act in an auxiliary manner by facilitating antigen processing or presentation, or by liberating factors which modify the various manifestations of the immune response. A variety of interactions between T and B cells and between lymphocytes and accessory cells have been described in both cellular and humoral immunity. Antigen-activated T cells produce factors with various activities: some are involved in recruiting inflammatory cells, others activate macrophages and enhance their microbicidal activities, and others modify B-cell responsiveness either by facilitating or suppressing it. These factors are instrumental in T-cell regulation of immune responsiveness. Antibody produced by B cells also plays a role in immuno-regulation, acting either as an immunopotentiating influence or as a negative feedback, e.g. when complexed with antigen, turning off the response of T or B cells. A detailed knowledge of the precise manner in which cells involved in immunity are regulated is essential for an understanding of how the foetus, an essentially "foreign transplant", can survive to term in its immunologically mature "alien" host.
Animals↗
Nature of cold-reactive antibodies to lymphocyte surface determinants in systemic lupus erythematosus.
Antilymphocyte antibodies in serum from patients with systemic lupus erythematosus (SLE), as detected by microcytotoxicity and indirect immunofluorescence, were predominantly cold reactive and of the IgM class. These IgM antibodies were most active at 4 degrees C. IgG antibodies were infrequent, and were only minimally lymphocytotoxic. Most sera were cytotoxic for autologous lymphocytes and were equally reactive with normal and SLE lymphocytes, as well as with B- and T-cell preparations. Separate T- and B-cell specificities, which appeared not to be related to HL-A determinants, were identified by differential absorption experiments. The functional significance of these antilymphocyte antibodies is discussed.
Animals↗
Acute lymphoblastic leukaemia: a heterogenous disease.
By using several techniques to detect surface markers on T and B lymphocytes, 11 cases of acute lymphoblastic leukaemia (A.L.L.) were studied. In four cases an insignificant number of markers were detected on the lymphoblast populations. In one case a significant number of blasts formed both sheep red blood cell rosettes and Fc rosettes, suggesting a T-cell origin for the neoplastic cells, and in another case the presence of Fc and C3 receptors on the lymphoblast population indicated a B-cell origin. In a further five cases 14-43% of the blasts had detectable surface immunoglobulin. It is concluded that A.L.L. is a heterogeneous disorder, some cases failing to express surface markers and others having either a T-or a B-lymphocyte origin or both.
Adolescent↗
Long term hazards in immunological methods of fertility control.
Long term problems associated with future immunological methods of fertility control include the following: (1) reversibility, (2) unscrupulous use, (3) unphysiological intervention giving rise, among other possibilities, to carcinogenesis, (4) deleterious genetical selection operating on antigens, and (5) deleterious genetical selection operating on the immune response. The first three of these constitute a hazard to individuals, and the last two to populations. None is considered to constitute a threat so serious as to inhibit further research on the subject. We should keep under review future developments in relevant areas of immunology, including particularly cell-cell cooperation as a mechanism in autoimmunity, and immune response genes as the objects of immunoselection. It will be important also to come to terms with the social, political, and economic consequences of any cheap, widely-applicable form of birth control, such as might develop from immunological research. The possibility is raised of wide-spread immunisation against a synthetic immunological determinant, as an aid to fertility control. Another possibility is to make women grandchildless.
Animals↗
[The lymphocyte cytotoxicity test in tumor immunology (author's transl)].
The cytotoxic action of lymphocytes on cancer cells in vitro indicates sensitization of the patient against his own tumor. The technical difficulities of this test and possibilities of standardization and simplifying the procedure are discussed. Critical steps are isolation of lymphocytes and culturing target cells without loosing their specific antigenic structure. The need for specificity controls both for lymphocytes and tumor cells is emphasized. Labelling tumor cells with isotopes represents a major improvement in evaluating the result. The role of thymus- and bone marrow-dependent lymphocytes as well as blocking factors in the serum of tumor patients can be analyzed in the cytotoxic assay. A better understanding of these mechanisms may facilitate a therapeutic approach by manipulating the interaction of tumor cells and host.
Animals↗
Ontogeny of lymphoid cell surface determinants in the chicken.
Five antigenic lymphoid cell surface determinants (LCSD) were detected in hatched chickens using specific antisera. These LCSD were: thymus-specific surface determinants, bursa-specific non-immunoglobulin determinants, IgM-specific determants, IgG-specific determinants, and IgA-specific determinants (ASD). Viable cell suspension of embryonic yolk sac, bursa, thymus and spleen were tested by means of indirect or direct immunofluorescent staining procedures for the presence and frequency of LCSD during maturation. Experiments performed with liver cells. brain cells and red blood cells of embryos confirmed the specificities of the antisera used for determinants present on cells of lymphoid tissues. The results showed LCSD to occur on yolk sac cells on the 5th to 7th embryonic day (ED). This suggests the presence of a stem cell pre-committed for the lymphoid cell line already in the yolk sac. Furthermore, findings are reported indicating the presence of distinct lympoid stem cell populations or maturation stages in the yolk sac, which may be responsible for either populating the thymus or the bursa. The finding of ASD-bearing cells early in ontogenesis of the lymphoid system suggests the presence of two specificities in anti-chicken IgA sera, one of which may be directed against an antigenic site on a rudimentary immunoglobulin molecule, which becomes lost or hidden in later maturation. Studies on the bursa and the thymus show that covering, hiding, or loss of antigenic determinants plays an important role in lymphoid cell differentiation. Furthermore, the spleen is reached by B-determined stem cells as early as the bursa, but these stem cells seem not to proliferate in the former to any considerable extent until hatching. Finally, the sequence of the appearance of immunoglobulin classes as proposed by other authors is confirmed with reservaitons concerning IgA, and it is suggested that immunoglobulins are detectable earlier on cell surfaces than intracytoplasmatically.
Animals↗
Immunofluorescent studies on antibodies directed to a buried membrane structure present in lymphocytes and erythrocytes.
Brief digestion of human peripheral blood lymphocytes by vibrio cholera neuraminidase (VCN) revealed hidden components of the membrane. Autologous human serums contained antibodies directed to these components that were readily demonstrated by immunofluorescence. Antibodies of similar specificity were found in all normal serums. The antibodies were principally of the IgM variety with lesser amounts of the IgG class present. They were equally active at 4 degrees C and 37 degrees C. The VCN revealed membrane determinants were present in normal B and T lymphocytes, monocytes, lymphocytes of patients with chronic lymphatic leukemia and cells of lymphoid lines. The newly revealed determinants slowly disappeared upon culture of the lymphocytes. These hidden components were similarly demonstrated in erythrocyte membranes and represent the T antigen long known for the red blood cells. Absorption by either VCN treated autologous lymphocytes or erythroyctes removed all of the antibodies capable of reacting with both cell types. Absorption by VCN digested isologous lymphocytes removed all reactivity with autologous lymphocytes.
Absorption↗
Characterization of human B lymphocyte specific antigens.
Anti-human B cell serum (ABS) was developed by sequentially absorbing a rabbit anti-human tonsil serum (AHTS) with human red cells, liver, serum, and thymocytes. AHTS was also absorbed quantitatively with tissues and cells from different sources. ABS was nontoxic for thymocytes but lysed the majority of chronic lymphocytic leukemia (CLL) cells. This also killed a number of tonsil and blood lymphocytes which bound erythrocyte-antibody-complement complexes but not sheep erythrocytes. In further studies, it was shown that phytohemagglutin-responsibility of peripheral blood lymphocytes was not affected by treating them with ABS and complement. Anti-B cell activity of AHTS was not changed by absorption with thymus, liver, kidney, and brain tissues but absorbed with tonsil and CLL cells. These data confirm the B cell specificity of ABS. Indirect immunofluorescence was carried out on tissue sections of human tonsils and lymph nodes, which indicated that ABS-reactive cells were concentrated in lymphoid follicles including germinal centers, while plasma cells and cells located in the thymus-dependent area were essentially devoid of immunofluorescence.
Absorption↗