摘要:

AbstractPrevious studies from this laboratory have revealed an antigenic site located on the variable domain of the λ2 light chain of BALB/c myeloma protein 315 (the Vλ2315site). This site is recognized by conventional carrier‐specific T helper cells (Th) of BALB/c mice and is expressed on both the free and assembled Vλ2315domain. The present work defines two new antigenic sites associated with murine λ chains. The first site was associated with free λ1‐chain of myeloma protein J558. It was recognized by splenic Thfrom animals that had been primed with free λ1J558in complete Freund's adjuvant; when transferred to irradiated animals the primed Thresponded to a boost with (4‐hydroxy‐5‐iodo‐3‐nitro‐phenyl)acetate (NIP)‐free λ1J558in saline, but did not respond to NIP‐complete J558 or NIP‐free λ2315. Priming with complete J558 failed to elicit Ththat responded to NIP‐free λ1J558. This determinant was therefore only expressed on the free (as opposed to the assembled) form of λ1J558, and it was not shared with free λ2315. The second antigenic site was shared between free λ1J558and free λ2315. It was defined by free λ2315‐primed Thwhich responded to a boost with NIP‐free λ1J558. Since priming with free λ1J558did not elicit Ththat recognized NIP‐free λ2315, the cross‐reaction was undirectional. The free λ2315‐primed Thfailed to respond to the complete J558, and M315‐primed Thfailed to respond to NIP‐free λ1J558, indicating that the second (cross‐reactive) antigenic site, like the first, was only expressed on free λ chains. Completely reduced and alkylated (unfolded) free λ1J558and free λ2315chains elicited Ththat recognized native (folded) free chains.Thus, free λ1J558bears two antigenic determinants recognized by Th, one private and a second shared with free λ2315. λ2315also bears two determinants, a cross‐reactive one on free λ2315shared with free λ1J558, and a private one located on the Vλ2315domain of the complete M315.The discussion is focused on possible explanations for the quenching of the two new λ chain determinants upon light‐heavy chain assembly and why

ISSN:0014-2980    

DOI:10.1002/eji.1830130502

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractThe effect of cyclosporin A on the induction and activation of B memory cells by thymus‐independent (TI) antigens was investigated. Studies were carried out in C57BL/6 mice, a strain in which TI.1 trinitrophenyl‐lipopolysaccharide (TNP‐LPS) and TI.2 dinitrophenyl‐(DNP)‐Ficoll antigens can elicit a secondary response. Evidence is presented that cyclosporin A does not adversely affect the primary or secondary response to TNP‐LPS. In contrast, this fungal metabolite prevents the triggering of virgin B lymphocytes and TNP‐LPS‐induced memory cells by DNP‐Ficoll. Cyclosporin A does not interfere with the generation of hapten‐specific B memory cells by TNP‐LPS or DNP‐Ficoll. These findings are discussed in terms of B cell lineages leading to antibody‐forming cell pr

ISSN:0014-2980    

DOI:10.1002/eji.1830130503

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractThis study was undertaken to determine whether and by what means particles which induce granulomatain vivocan affect murine spleen lymphoproliferative and antibody responsesin vitro. Particles of silica, talc, Bentonite orC. parvumcells inhibited lipopolysaccharide‐ or concanavalin A‐stimulated proliferation and sheep red blood cell‐induced antibody responsein vitro. The inhibition required at least 48 hours exposure of the cells to the particles. The late onset of inhibition and its reproducibility at different cell or mitogen concentrations implicated particle‐induced injury to both phagocytes and lymphocytes. Either α‐tocopherol or 2‐mercaptoethanol prevented the particle‐induced inhibition of spleen cell responses. α‐Tocopherol and 2‐mercaptoethanol have in common the capacity to protect cells against membrane lipid peroxidation. The inhibitory peroxidative process(es) implicated by these studies are most likely attributable to: (a) stimulation of oxidative metabolism of phagocytic cells by particles; and (b) iron‐catalyzed peroxidation directly by the particles. These data may be relevant in understanding the pathogenesis of and devising therapeutic approaches toward various gra

ISSN:0014-2980    

DOI:10.1002/eji.1830130504

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractThe ability of human lymphocytes to bind antigen was studied by direct binding of125I‐labeled streptococcal protein antigen, followed by autoradiography. T‐enriched lymphocytes depleted of adherent cells and B cells showed specific binding of125I‐labeled streptococcal antigen (SA) at 4°C and in the presence of sodium azide. Further depletions of the T‐enriched population by the monoclonal T4 or T8 antiserum and complement revealed that the antigen‐binding T cell is T4−, T8+. This was confirmed by positive selection of T8 cells, by rosetting with ox red blood cells and by the binding of SA byin vitroinduced suppressor but not helper cells. Antigen specificity of binding to the suppressor cells was established by complete inhibition with the SA but no inhibition with keyhole limpet hemocyanin. A characteristic dose‐response of binding 1 or 10 ng SA to HLA‐DRw6 lymphocytes and 1000 ng SA to DR4,1,2,3 or 5 lymphocytes was found. A comparison of the dose‐responses of antigen‐binding T+suppressor cells with those of helper and suppressor functions showed that the dose of SA which binds to suppressor cells is similar to the dose required to induce helper but not suppressor function. A plausible interpretation of these observations is that the T8+antigen‐binding suppressor cells might function as “contrasuppressor cells” which compete successfully for the membrane receptors of helper cells, thereby preventing suppression by the major

ISSN:0014-2980    

DOI:10.1002/eji.1830130505

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractWhen normal human B cells from blood, tonsil or spleen are cultured with 20–30% autologous or allogeneic T cells and mitogen, the majority of cells rosette with sheep erythrocytes (E) after 3–5 days in culture. These E+cells are of transformed appearance and several points indicate that many are derived from B cells. Some simultaneously possess surface immunoglobulin (sIg) or a B cell antigen [detected with BA1 monoclonal antibody (mAb)] and E receptor. Many do not stain with anti‐T cell mAb (UCHT1, OKT4, OKT8), while cultured T cells continue to express these antigens. Furthermore, many E+cells appear when the original T cells have been irradiated. All the cultured E+cells stain with OKT11, an mAb against the E receptor, and their positivity cannot therefore be attributed to mitogen‐induced nonspecific stickiness. The E positivity of the B cells was shown to be endogenous since passive acquisition of E receptor shed by T cells was excluded in a number of ways; no phenotypic changes were observed when supernatants from cultures containing many E+sIg+non‐T cells were added to B cells, or when the B and T cells were separated by a Millipore membrane; and E receptor was re‐expressed after stripping with trypsin or pronase. The intimate presence of T cells is essential for the expression of E receptors by B cells, and this helper capacity was shown to reside within the OKT4‐defined helper T cell subpopulation. The significance of the expression of E receptor by B cells is discussed in relation to the recentin vitroandin vivodemonstration of E+sIg+cells in certain leukemias and in relation to the specificity of E rosetting as a mark

ISSN:0014-2980    

DOI:10.1002/eji.1830130506

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractHuman natural killer (NK) cells expressing the HNK‐1 differentiation antigen were established in long‐term tissue culture for over 3 months. The fluorescence‐activated cell sorter‐purified HNK‐1+cells required both phytohemagglutinin and exogenous interleukin 2 to propagate in long‐term culture. After 2 weeks of culture, virtually all of the growing cells exhibited the surface membrane phenotype associated with immature HNK‐1+cells, since they simultaneously expressed the HNK‐1, Leu‐4 and Leu‐2a but lacked the M1, Leu‐3a and T6 antigens, and Fcγ receptors. They exhibited a lymphoblastoid appearance, contained cytoplasmic granules, and exhibited spontaneous cytotoxic function against a broader spectrum of target cells than did fresh HNK‐1+cells from the same donor. Cultured HNK‐1+cells lacked antibody‐dependent cell‐mediated cytotoxic (ADCC) function, while fresh HNK‐1+were fully capable of ADCC function. On the other hand, cultured HNK‐1−cells were lymphoblasts without cytoplasmic granules or NK cytotoxic function. The cultured HNK‐1+cells gradually lost their HNK‐1 antigen expression over time, although the expression of other surface antigens (e.g., Leu‐4 and Leu‐2a) was unchanged. With prolonged culture (>2 months), they also exhibited decreasing cytotoxic function and a diminished number of cytoplasmic granules. They were eventually indistinguishable from HNK‐1−cells after 3 months of culture. These observations were not influenced by adding interferon‐γ to the cultures. The results demonstrate that the immature form of NK cells (that express T cell antigens) preferentially proliferate in long‐term cultures whe

ISSN:0014-2980    

DOI:10.1002/eji.1830130507

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractMononuclear cells isolated from human cord blood (CBL) of full‐term neonates were stimulatedin vitrowith a dose range of T cell‐dependent antigens,i.e.ovalbumin or sheep erythrocytes, and tested for the capacity to mount an antigen‐specific plaque‐forming cell (PFC) response. Both of the antigens used induced in CBL a PFC response with the same kinetics of PFC formation and of the same magnitude as found in cultures of adult peripheral blood lymphocytes (PBL).However, optimal PFC responses in CBL were obtained at a hundredfold lower concentration of the antigens compared with the optimal antigen doses for the induction of a PFC response in adult PBL. This phenomenon was further investigated with respect to the antigen dose dependency of the activation of neonatal B cells and neonatal regulatory T cells. The induction of a PFC response in CBL at antigen concentrations that were suboptimal for adult PBL showed a correlation with the particular antigen dose requirements for the activation of B cells and T helper cells in neonates. Furthermore, the findings suggest that the decrease of the PFC response in CBL stimulated with supraoptimal doses of antigen was not caused by the induction of unresponsiveness at the B cell level or by interference of pregnancy‐associated substances with the PFC response, but was rather the result of the activation of antigen‐specific T suppressor cells. Neonatal T suppressor cells were activated at antigen concentrations that generated T helper activity in the adult. Thus, although neonatal B cells possess the intrinsic capacity to mature into antigen‐specific PFC, the conditions for effective activation of neonatal T cells regulating the B cell response differ from those for the activation of adult regul

ISSN:0014-2980    

DOI:10.1002/eji.1830130508

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractAntisera were raised in rabbits against L chains, isolated from mouse myeloma protein MOPC21 (γ1,x, Vx15group). Specific antibodies for the V and C domain of MOPC 21 L chain were obtained by cross‐immunoadsorption of the antisera. The pure anti‐V and anti‐C antibodies were fixed on diazocellulose and used as immunosorbents. The inhibitory capacity of L chain‐monomers and dimers isolated from the L chain preparation was compared to that of intact IgG1using binding inhibition of125I‐labeled IgG1on the antibody‐containing immunosorbents. It was established that changes of IgG1quaternary structure influences the conformational state of the L chain V domain only. The inhibitory capacity of the V domain is 1000‐fold lower in L monomers, if compared with native IgG1, and only 10‐fold lower than in L dimers. The inhibiting capacity of the C domain, however, does not differ in L monomers and intact IgG1. Thus the conformational rigidity of the C domain co‐exists with conformational flexibility of the V domain on the same polypeptide chain. We tried to estimate the content of MOPC 21 VL‐like normal IgG in mouse serum of 6 inbred strains using antibodies against the VLdomain. Data obtained by inhibition of radioimmunoadsorption, indicate that in C57BL/6 mice 0.08% of normal serum Ig carries a VLregion which is idiotypically related to the VLof MOPC 21. In serum Ig of BALB/c mice th

ISSN:0014-2980    

DOI:10.1002/eji.1830130509

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractThymus cells from neonatal and infant mice were found to have a high capacity to prevent mortality from acute graft‐vs.‐host disease as compared with spleen cells from stable radiation chimeras. This suppressive capacity of thymocytes decreases with age after birth as was demonstrated by semi‐quantitative cell titrations. This suppressor activity is restricted to syngeneity of the graft‐vs.‐host disease‐including cells. The thymic suppressor cells are Thy‐1+and Lyt‐1+and IgG−and IgM−. They do not agglutinate with peanut agglutinin and have a high electrophoretic mobility.In vitroirradiation experiments showed that the suppressor cells are radiation sensitive. These results are compared with the available information on cells suppressing delayed‐type hypersensitivity reactions and those suppres

ISSN:0014-2980    

DOI:10.1002/eji.1830130510

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY

摘要:

AbstractMice were immunized with hapten [NIP, (4‐hydroxy‐5‐iodo‐3‐nitrophenyl)acetyl or TNP (2,4,6‐trinitrophenyl)] conjugates of Ficoll or pneumococcal polysaccharide type 14 (S14), and they were bled on days 10 or 14. Anti‐hapten and anti‐polysaccharide antibodies were determined from the sera or from fractions (IgM + IgA), IgG1, IgG2a, IgG3or IgG2hseparated by a gradual acid elution from protein A. Approximately one‐half of both anti‐hapten and anti‐polysaccharide antibodies was found in the IgM + IgA fraction. The subclass distribution of the IgG antibodies was dependent on the antigenic determinants. Polysaccharide antibodies were mostly in the IgG3fraction (36–62%) and in the IgG1fraction (18–36%). Hapten IgG antibodies were mostly in the IgG1fraction (38–74%); each of the other three subclasses contributed the average of 13%. These results provide the first evidence that antibodies to different determinants of one antigen have grossly diff

ISSN:0014-2980    

DOI:10.1002/eji.1830130511

出版商:WILEY‐VCH Verlag GmbH    

年代:1983

数据来源: WILEY