摘要:

AbstractThe affinity of serum antibodies produced by selectively bred lines of mice [high affinity, low affinity, low nonmaturing (N/M)] injected with T‐dependent [human serum albumin (HSA), dinitrophenylated bovine γ‐globulin (DNP‐BGG)]and T‐independent (DNP‐Ficoll) antigens in saline and adjuvant has been determined. The lines of mice differ significantly in the affinity of antibody produced to T‐dependent antigens injected in saline but not to the T‐independent antigen. Unlike mice of the high and low‐affinity lines, low‐affinity N/M mice failed to show affinity maturation to HSA and DNP‐BGG injected in Freund's incomplete adjuvant. However, low‐N/M mice responded to DNP‐Ficoll injected in adjuvant by the production of antibody of affinity comparable to that produced in the other lines and with a similar maturation in affinity. Carrier priming resulted in the suppression of anti‐hapten antibody affinity in all lines but low‐N/M mice showed significantly greater suppression late in the response to challenge. Low doses of cyclophosphamide produced a significant increase in affinity in low‐N/M mice. These results suggest that the failure of low‐N/M mice to show affinity maturation results from increased suppressor T cell activity. The availability of the selectively bred mice provides a useful model for the detailed study of the cellular basis of the control

ISSN:0014-2980    

DOI:10.1002/eji.1830160112

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractAdministration of 2,4,6‐trinitrophenylatedE. colilipopolysaccharide (TNP‐LPS) complexed with mouse IgG antibody to TNP specifically gave rise to a marked production of rheumatoid‐like factors (RF) in the recipient mice, in contrast to the low and nonspecific RF production via polyclonal B cell activation by the same dosage of LPS or TNP‐LPS alone. The RF activity induced by the LPS immune complexes was associated with both IgG and IgM and directed primarily to the Cγ2 region as judged by the heterophilic reactivity toward fragments of rabbit IgG. The results suggest that antibody molecules attached to LPS constitute novel epitopic groups on the mitogenic carrier and stimulate B cells in a specific manner to induce the autoan

ISSN:0014-2980    

DOI:10.1002/eji.1830160113

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractVarious model systems have been used to study isolated B cell response to receptor cross‐linking and to lymphokines. Although each model is useful it is advantageous to have continuous cell lines of nonmalignant antigen‐specific B lymphocytes to study antigen‐induced B cell function. We further studied the characteristics of the 2,4‐dinitrophenyl (DNP)‐specific continuous B lymphocyte lines which we previously described (J. Exp. Med.1983.157: 342). If the cell line lymphocytes are cultured with the antigen DNP‐Ficoll without the presence of T cell factors or filler cells they do not produce an immune response above background, but the addition of supernatant from EL4 lymphoma and irradiated normal spleen filler cells results in a 7‐ to 10‐fold increase in plaque‐forming cells. The kinetics of the immune response is the same as that seen with normal B cells. Each cell line has a majority of cells which are small surface (s)IgM−lymphocytes which have cytoplasmic IgM and react with 14.8 antibody. There are also large sIgM+‐bearing cells, which may be either in the resting or activated state. Some of the sIgM+cells also bear IgD and Ia antigens but they do not bear IgG. From these studies we conclude that the continuously growing antigen‐specific B cell lines can be a useful model t

ISSN:0014-2980    

DOI:10.1002/eji.1830160114

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractAfter establishing optimal conditions for measuring the membrane lipid packing density (“fluidity”) of chicken peripheral blood lymphocytes, the fluidity was modulatedin vitroby incubation in cholesterol or phospholipid (“active lipid”, AL)‐enriched serum‐free tissue culture medium. The effect of these lipids on mitogen responsiveness was then investigated, the aim being to determine whether the observed enhancement/suppression was membrane mediated,i.e.explainable by fluidity changes.Chicken peripheral blood lymphocytes exhibited no requirement for exogenous cholesterol; low concentrations did not affect the mitogen response while the higher concentrations, which induced a measurabledecreasein membrane fluidity, were usually mildly suppressive. Pre‐incubation did not increase this suppressive effect and we believe itnotto be membrane mediated.AL, at low concentrations which induced no changes in membrane fluidity, prolonged the phytohemagglutinin response, enhancement being evident onlyafterthe peak; we interpret this as a nutrient effect. At the higher concentrations, which induced large increases in fluidity, a transient enhancement was followed by suppression; suppression was delayed in onset when AL was added 4 h after phytohemagglutinin stimulation. It is therefore an early event which may be mediated through changes in memb

ISSN:0014-2980    

DOI:10.1002/eji.1830160115

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractUnselected IgM‐secreting hybridoma collections were established either from unprimed naturally activated newborn spleen cells or from mitogen‐stimulated adult B cells. These were then screened for reactivity with a panel of monoclonal anti‐idiotypic antibodies and haptens. While the finding of hapten‐specific antibodies was equally frequent in either collection, newborn antibodies reacted at least 10 times more frequently with the anti‐idiotypic reagents. The reactivity patterns of individual antibodies readily demonstrated the overall specificity of these V‐region interactions. Since some of the idiotopes screened are characteristically not expressed in immune responses by the strains analyzed, and are in fact not expressed in the adult induced hybridoma collection, we explain these findings by a unique property of the set of natural (newborn) antibodiesi.e.the high levels of idiotypic connectivity previously described within this

ISSN:0014-2980    

DOI:10.1002/eji.1830160116

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractExperiments were undertaken to localize in the lipopolysaccharide (LPS) the minimal structural determinants sufficient to initiate the signal leading to interleukin 1 (IL 1) secretion by human monocytes. Our results clearly demonstrated that this signal is triggered by structures present in the so‐called inner‐core region which chemically consists of 2‐keto‐3‐deoxy‐wD‐manno‐octulosonic acid (KDo) and heptose in many LPS of gram‐negative bacteria. Thus, the isolated polysaccharide region ofBordetella pertussisendotoxin as well as fragments derived therefrom containing the reducing KDO unit were able to induce similar levels of IL1 induction as the native LPS. Similarly, the trisaccharide α‐D‐manno‐heptopyranosyl‐(1–3)‐α‐D‐manno‐heptopyranosyl‐(1–5)‐3‐deoxy‐D‐manno‐octulosonic acid (hep‐hep‐KDO), representative for the inner‐core region of a large number of enterobacterial LPS, was a very potent IL 1 inducer. Neither KDO monosaccharide, nor the α‐(2–4)‐linked 3‐deoxy‐D‐manno‐octulosonic acid disaccharide isolated fromSalmonellarough‐form LPS promoted the signal indicating that the minimal structure of endotox

ISSN:0014-2980    

DOI:10.1002/eji.1830160117

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractMouse B cells cultured with either phorbol myristate acetate (PMA), or with Ca2+ionophores enter a transitional activated state, between quiescence (G0) and G1, but do not synthesize DNA. It is shown here that the combination of PMA plus the ionophore ionomycin induces resting B cells to synthesize DNA, but not to secrete antibody. B cells from CBA/N mice carrying thexiddefect, and those from the lipopolysaccharide‐unresponsive C3H/HeJ strain also respond to this combination. Suboptimal doses of the two stimuli synergize with B cell‐stimulating factor 1 in promoting proliferation of resting B cells, but the co‐mitogen does not substitute for type II B cell growth factor in the BCL1lymphoma. Furthermore, (as predicted) the combination of these two agents does not induce the breakdown of inositol phospholipids in B cells. These data are consistent with the hypothesis that elevation of intracellular Ca2+(by the ionophore), plus activation of protein kinase C (by PMA) leads to DNA synthesis in B cells. The combination of Ca2+ionophore and PMA thus appears to essentially mimic the biochemical effects of ligation of surface immunoglobulin receptors on B cells, by providing the two second messengers normally emanating from the receptor‐mediated breakdown of polyphosphoino

ISSN:0014-2980    

DOI:10.1002/eji.1830160118

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractSeventeen monoclonal anti‐2‐phenyloxazolone antibodies from the early (day 7) primary response were partially sequenced with an mRNA method. Ten antibodies expressed the VH−Ox1 gene. The remaining seven express at least four but probably six different germ‐line VHgenes belonging to Dildrop's groups 1, 5, 6 and 7 (Immunol. Today1984.5: 85). Two of them have been met before in other antibodies, one (group 6) in J606 and the other (group 7) in antibodies to the influenza virus hemagglutinin.Eleven kappa chains were partially sequenced and five of them (all VH−Ox1 antibodies) express the Vx−Ox1 gene. One expresses another germ‐line gene of the Vx−Ox1 family, one the Vx89.4 gene, three the Vx45.1 gene and one a new Vxgene. The Vx45.1 gene was found to form anti‐phox antibodies with two new VHgenes.The frequency of somatic mutations in day 7 antibodies was estimated by comparing germ‐line sequences and antibody sequences. It is low (one mutation per 2500 nucleotides sequenced), twenty times lower than in antibodies obtained a week later. Two anti‐idiotype antisera (495 and 260) are useful in the typing of monoclonal antibodies. 260 bound only to antibodies coded by both VH−Ox1 and Vx−Ox1 genes. 495 bound strongly to antibodies coded by the VH−Ox1 gene and weakly to antibodies coded by the (related) VH101 gene regardless

ISSN:0014-2980    

DOI:10.1002/eji.1830160119

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractEarly anti‐phenyloxazolone antibodies of B ALB/c mice include a subset that bears the nearly or totally unmutated VH−Ox1 sequence. A fraction of this subset also bears the nearly or totally unmutated Vx−Ox1 sequence. The whole subset is recognized by an anti‐idiotype serum 495 and the VH−Ox1/Vx−Ox1 fraction also by another anti‐idiotype serum 260.Frequencies of the VH−Ox1 subset and its Vx−Ox1 fraction in early IgM and IgG antibodies were determined by typing hybridomas with anti‐idiotype antisera. The whole subset appears to make up approximately one half of IgG antibodies, two thirds of this being 495+/260+in both isotypes. IgM data are less certain but the same frequencies may be valid.Affinities of 495+/260+antibodies ranged from 1.3 × 106to 11 × 106, affinities of 495+/260−antibodies from 0.47 × 106to 1.1 × 106, and affinities of doubly negative antibodies were less than 0.41 × 106. High affinity is probably an explanation for the high proportion (one third) of the 495+/260+antibodies in the early response. Doubly negative (and low‐affinity) hybridomas may not have been classified as producers of phenyloxazolone antibodies in earlier studies, and this could explain the still higher reported frequency (73%)

ISSN:0014-2980    

DOI:10.1002/eji.1830160120

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractThe mutantlprgene causes a generalized massive T cell proliferation and an associated autoimmune disease in mice. ThelprT cells bear unusual membrane phenotypes and play a causative role in the pathogenesis of autoimmune disease through excess production of some lymphokines. Therefore, the “aberrant” T cells inlprmice may be normal regulatory T cells in non‐lpr‐bearing mice, if nonproliferative. We thus attempted to produce a xenogeneic monoclonal antibody (ALP‐1) directed against thelprT cells. The ALP‐1 monoclonal antibody reacted with the antigen Lp‐1 distributing on about one half of the proliferating lymph node cells from MRL/Mp‐lpr/lprmice but not on the cells from non‐lpr‐bearing mice. Nevertheless, a significant number of Lp‐1+cells appeared in the lymph node and spleen cells from these normal mice afterin vitrostimulation with mitogens. Functional studies revealed that either the treatment with ALP‐1 plus complement of the antigen‐primed splenic T cells from non‐lpr‐bearing mice or the addition of ALP‐1 alone all but completely abolished the development of plaque‐forming cells against sheep red blood cells in T‐B cell co‐culture. Pretreatment of spleen cells with ALP‐1 plus complement, however, did not affect otherin vitroT cell functions such as mitogen‐induced proliferative responses, interleukin 2 production, response in mixed lymphocyte culture (MLC) and the MLC‐induced cytotoxic T cell activities. Thus, Lp‐1+T cells in normal mice are unique T cells that may play an importa

ISSN:0014-2980    

DOI:10.1002/eji.1830160121

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY