摘要:

AbstractRecent studies from other laboratories have shown that concanavalin A (Con A) acts at two separate steps in polyclonal T cell activation: interleukin 2 (IL2) production, and induction of responsiveness to IL2. Using a combination of techniques for the depletion of accessory cells from lymph node T cells, we have investigated which of these steps, if not both, is responsible for the known requirement for accessory cells in the Con A response. It was found that with increasing T cell purification, first the ability is lost to produce sufficient levels of endogenous IL2, whereas induction of IL2 responsiveness can still take place. Further removal of accessory cells however yields a population of resting T cells that cannot be induced by Con A to become IL2‐reactive. It was concluded that both IL2 production and induction of reactivity to IL 2 are accessory cell‐dependent eve

ISSN:0014-2980    

DOI:10.1002/eji.1830130103

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractThe study was undertaken to elucidate some functional characteristics of T cell subsets in human cord blood. A comparison of the cellular interactions involved in thein vitroregulation of pokeweed (PWM)vs. Epstein‐Barr virus (EBV)‐driven B cell differentiation was donein vitroin short‐term cultures of lymphocytes from newborns or adults. T cell subsets were isolated using the monoclonal antibodies OKT4+and OKT8+.OKT4+but not OKT8+T lymphocytes from adults as well as neonates suppressed EBV‐induced immunoglobulin (Ig) secretion of B lymphocytes from adults. This inhibition was mediated through gamma‐type interferon (IFN‐γ). B cells from newborns were not inhibitable by OKT4+lymphocytes as a result of their insensitivity to IFN‐γ.Helper activity for PWM‐induced Ig secretion was exclusively contained within the OKT4+population from adult T cell donors. This function was normally not detectable in any of the neonatal T cell subsets. OKT8+cells from both adults and neonates suppressed PWM‐induced Ig secretion, but required the collaboration with cells within the OKT4+population. The suppressor activity in the PWM system was not IFN‐γ‐mediated.Thus, suppressor functions for EBV‐vs. PWM‐induced Ig synthesis were mediated through different pathways. There was no evidence of a unique suppressor system in the newborn. In the neonate, suppressor T cell activities are developed before T helper functions, a circumstance for which there

ISSN:0014-2980    

DOI:10.1002/eji.1830130104

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractTo study the idiotypes (Id) of the humoral response to H‐2Ldantigens, xenogeneic antisera were produced to three independent monoclonal antibodies, recognizing Lddeterminants H‐2.64 or 65. The reactivity of each of these anti‐Id was specific for the immunizing antibody, no cross‐reactions among the three anti‐L hybridomas being detectable. Antisera produced in BALB/c H‐2dm2mice hyperimmunized with BALB/c tissue were examined for the presence of cross‐reactive Id (IdCR). When the ability of these anti‐Id to inhibit the binding of alloantibodies to Ldsplenic antigens was tested, a broadly shared Id was detected by one anti‐Id (anti‐23‐10‐1S). The shared Id represented between one‐fourth and one‐half of the total anti‐Ldhumoral response and was found in every BALB/c H‐2dm2anti‐BALB/c serum tested. The IdCRwas limited to those alloantibodies reacting with the determinant H‐2.65 which corresponds with the serologic reactivity of monoclonal antibody 23‐10‐1S. The other two anti‐Id did not detect components of the anti‐Ldhumoral response, even though one of these was made against monoclonal antibody 30‐5‐7S which also detects serologic specificity H‐2.65. The detection of a IdCRin anti‐Ldresponses stands in contrast to our previous failure to detect IdCRin anti‐H‐2Kkresponses. Among the possible reasons for this contrast are (a) the fact that 23‐10‐1S is an IgM antibody, whereas the anti‐H‐2Kkantibodies studies were IgG; (b) the chance occurrence of anti‐H‐2 hybridomas with dominant Id and (c) the possibility that the anti‐Ldantibody

ISSN:0014-2980    

DOI:10.1002/eji.1830130105

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractThe polypeptide chain composition of class II antigens from LEW rat spleen cells was studied utilizing cross‐reactive mouse alloantiserum A. TH anti‐A.TL (specificity anti‐Iak) and the monoclonal antibodies MRC‐OX6 and MRC‐OX3 for immunoprecipitation. Two‐dimensional gel mapping of A. TH anti‐A. TL immunoprecipitates revealed that, as in the mouse, two groups of class II antigens exist corresponding to I‐A and I‐E locus equivalent structures. In the absence of reducing agents three monomeric chains α, 36 kDa (p36); γ, 33 kDa (p33); and β, 23 kDa (p23), were detected for I‐A equivalent antigens, whereas I‐E equivalent molecules separated into five monomeric chains: α, 37 kDa (p37); γ, 33 kDa (p33); and three β chains 28 (p28), 26 (p26) and 24 kDa (p24). One strong dimer component of disulfide‐linked γ chains was found to be associated with products of both loci. Although slightly different in molecular weight, γ chain corresponds to the nonpolymorphic murine invariant chain Ii.Both monoclonal antibodies recognized rat homologues of the murine I‐A products. Extensive sequential criss‐cross‐immunoprecipitation with subsequent 2‐dimensional O'Farrell analysis indicated that (a) MRC‐OX6 precipitated molecules which were not recognized by MRC‐OX3 andvice versa; (b) MRC‐OX6 precipitated a three‐polypeptide chain complex composed of the polypeptides p36, p33 and p23; (c) MRC‐OX3 precipitated a two‐chain complex composed of p36 and p23; and (d) the respective heavy (α) and light (β) chains of both complexes possess very similar physicochemical parameters, suggesting

ISSN:0014-2980    

DOI:10.1002/eji.1830130106

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractThree alloreactive T cell clones are described which reveal a new lymphocytestimulating determinant (Lsd) controlled by a gene on chromosome 1 of the mouse but different from and possibly centromeric to Mls. Two clones were originally isolated as anti‐H‐2b‐specific and showed and retained cross‐reactivity to Lsd (clone OD3, BALB/c anti‐C57BL/6; clone KB37, B10.BR anti‐C57BL/10). The third clone (BD7, C57BL/6 anti‐CBA/J) was probably originally directed against Lsd. So far, Lsd is only characterized by stimulation of T cell proliferation, and its physiological function is

ISSN:0014-2980    

DOI:10.1002/eji.1830130107

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractA number of human B lymphoblast cell lines were tested to find a suitable model for induction of immunoglobulin‐secreting cells (ISC) by T cell replacing factor (TRF). Partially purified TRF was size fractionated from the conditioned medium of irradiated (1000 rds) human spleen cells stimulated with pokeweed mitogen. IgM line SKW 6 showed high levels of TRF‐stimulated immunoglobulin secretion and was chosen for cloning experiments. Clone 11 had a very low level of ISC with or without TRF (less than 0.1% ISC). Clone 4 had low background numbers of ISC (0.2%) and showed the highest degree of stimulation by TRF (to 6% IFC). High secreting clone 8‐2 (6%) was not stimulated significantly by TRF. These clones had the same HLA‐DR antigens, and their levels of ISC and sensitivity to TRF were relatively stable over three months of observation. The TRF preparation also had strong helper activity for normal peripheral blood B cell differentiation. TRF activity for both normal B cells and clone 4 cell line was absorbed by all 3 clones, but not by a pre‐B line. This suggests that the effector molecules for normal B cell and cell line differentiation were the same. The three typical clones corresponding to nonresponding, responding, and high rate‐secreting B cells provide basic models for analyzing B cell receptors for TRF and the biochemical effects of TRF during B cell diffe

ISSN:0014-2980    

DOI:10.1002/eji.1830130108

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractThe effect of fractionated total lymphoid irradiation (TLI) on the maturation of B cells was examined in mice. At various times after irradiation of the mice, their spleen cells were tested for the mitogenic responses to dextran sulfate and lipopolysac‐charide. In parallel the cells were stained with fluorescent anti‐Thy‐1 and various anti‐Ig antisera, and were analyzed on a fluorescence‐activated cell sorter (FACS). By comparison with normal spleen cells the cells of TLI‐treated mice gave a high response to dextran sulfate and a low response to lipopolysaccharide. FACS analysis revealed that TLI‐treated spleen contains elevated numbers of B cells bearing high IgM and low IgD on the surface. The B cells of TLI‐treated mice retained these immature characteristics even two to four months after the last irradiation. These findings indicate that TLI causes a longlasting blockage in B cell matur

ISSN:0014-2980    

DOI:10.1002/eji.1830130109

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractTotal lymphoid irradiation (TLI) results in long‐lasting changes in the characteristics of both T and B cells suggestive of arrested maturation. A characteristic feature of immature B cells is their high susceptibility to tolerance induction. This study examines the susceptibility to tolerance to bovine serum albumin (BSA) of TLI‐treated mice. Two experimental protocols were designed. In the first, tolerance to BSA was induced in TLI‐treated adult (BALB/c × C57BL/6)F1mice, and the ability of B cells of those mice to respond to BSA was assessed in an adoptive transfer system. In the second experimental protocol, tolerance was induced in adoptive hosts reconstituted with purified B cells originating from TLI‐treated mice and with splenic T cells of normal, untreated mice. Results obtained in these two systems clearly demonstrated that splenic B cells of TLI‐treated mice are highly susceptible to tolerance induction. This high susceptibility of B cells is linked neither with the elevation of immature T cells nor with induced T suppressor cells which arise due to the long‐term malfunction of the thymus. Tolerance could be induced in TLI cells even 4 months after termination of the treatment. Thus, maturation processes of B cells in TLI‐treated mice are arrested for long p

ISSN:0014-2980    

DOI:10.1002/eji.1830130110

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractInjection of lipopolysaccharide into adult mice results in a rapid increase in the number of splenic IgM‐secreting plaque‐forming cells (PFC) so that by 60 h they represent roughly 20 times those present in normal mice. Although inhibited for the first two days, IgG3, IgG2band IgG2aPFC are later selectively stimulated and, by 110 h, they reach numbers that are 100, 40 and 30 times, respectively, those of normal mice. IgG1PFC are stimulated only marginally and 48 h after the maximal responses of the other IgG subclasses. IgA PFC are selectively inhibited and drop to 20% of normal numbers 4 days after injection. The ability of lipopolysaccharide to selectively stimulate B cells for the production of IgG3, IgG2band IgG2awas further substantiated by studying athymic mice, and by using adoptive cell transfers that overcome regulatory influences limiting these responses in intact mice. Under these conditions, 16% of all spleen cells are PFC and up to 85% of all Ig‐secreting cells are included in those three isotypes. Similar responses are also detected in bone marrow but they occur 24–48 h after the splenic responses, suggesting that bone marrow PFC are not induced in situ. These results demonstrate a selectivein vivoisotype commitment in response to lipopolysaccharide that is polyclonal and, therefore, independent of V region specif

ISSN:0014-2980    

DOI:10.1002/eji.1830130111

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractIn this study, the octapeptide hormone, angiotensin II (H‐Asp1‐Arg2‐Val3‐Tyr4‐Ile5‐His6‐Pro7‐Phe8‐OH; AII), and various AII homologues and analogues were employed as an antigen system to investigate the binding specificities of guinea pig antibodies. Using small, precisely defined peptides facilitates the comparison of the antigen‐binding repertoire of antibodies with the antigen specificities of T cells since unconju‐gated AII elicits both cellular and humoral immune responses. The T cell proliferative response has previously been shown to be exquisitely specific and under Ir gene control. In contrast, antibody binding, as reported here, was decidedly less specific and independent or the Ir gene control reported for the T cell proliferative response. Antisera from individual strain 2 or 13 guinea pigs immunized with either AII or [Val5]‐AII contained IgG antibodies that were highly restricted by isoelectric focusing but capable of binding either antigen with nearly equal efficiency, as determined by competitive inhibition studies in radioimmunoassays. The fine specificity of antibody binding was examined through the use of a series of AII homologues and analogues for competitive inhibition. The important residues for peptide‐antibody binding were Phe8, His6, Tyr4, and Asp1, since analogues with residue substitutions at these sites were much less efficient inhibitors. These results are discussed with respect to the differences in recognition of peptide antigenic dete

ISSN:0014-2980    

DOI:10.1002/eji.1830130112

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY