摘要:

AbstractA patient (Mia) with a monoclonal IgM(k) cryoglobulin (cryo IgM) developed additional heavy chain disease proteins of the γ3 subclass 8 years later. Biochemical studies of the cryo IgM indicated that the heavy chain was VHI, but the NH2‐terminal amino acid sequence of the light chain did not permit a definite assignment of its VKsubgroup. Two major fragments of the γ3 chain were distinguishable by electrophoresis in sodium dodecyl sulfate polyacryl‐amide gel. The smaller component (designated Mia F) had a molecular weight of approximately 30 000 and the larger component (designated Mia S) 35 000. Both fragments had G3m(21) and G3m(27) allotypic determinants. These data and the NH2‐terminal amino acid sequence of the γ chain fragments suggested that Mia S consists of the major part of the γ3 hinge region plus the CH2 and CH3 domains of the γ3 chain, whereas Mia F may be derived from the former as a result of postsynthetic cleavage. The partial amino acid sequence of the Mia S fragment is homologous to the hinge region amino acid sequence of human γ3 chains reported in the literature, with only one amino acid difference out of the 11 residues compared. This difference may represent an allotypic difference within the γ3 subclass. Alternatively, the production of Mia S may have resulted from the accidental derepression of a “silent” constant region gene not expressed in no

ISSN:0014-2980    

DOI:10.1002/eji.1830080602

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractThe amino acid sequence was determined for residues 1 to 88 and residues 110 to 147 for a rabbit light chain (4153‐I) with allotype b9 from a homogeneous anti‐streptococcal antibody. The amino acid sequence of the L chain from a second antibody (4153‐II) was also determined for residues 1 to 49 and 62 to 77. In spite of the large differences in constant region sequence between b4 and b9 L chains, the variable regions of these antibodies are quite similar to those reported for b4 L chains. Both chains bear a b9‐specific substitution (glutamic acid) at position 16. The 4153‐I chain also has substitutions at positions 70 and 81 that may be exclusive to variable regions of the L chains with the b9 allotype. These allotype‐associated VLstructural differences offer support to the notion that structural genes for the CLregion are either linked to distinct VLgene complexes or that certain V regions are expressed only in concert with certai

ISSN:0014-2980    

DOI:10.1002/eji.1830080603

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractBy separation of human blood lymphocyte suspensions on isotonic linear density gradients, fractions were obtained which differed in their responsein vitrotowards mitogens, antigens and allogeneic lymphocytes, as tested by incorporation of radioactive thymidine. Next, light (ρ1.067 g/cm3) lymphocytes were separated on discontinuous density, gradients and their reactivity tested to phytohemagglutinin, pokeweed mitogen, concanavalin A, purified protein derivative of tuberculin, a cocktail of antigens, and in the mixed lymphocyte culture (MLC). The light lymphocytes responded 1.6 to 6 times more strongly than the heavy lymphocytes (p<0.0005) to all stimuli tested. The spontaneous thymidine incorporation of the light lymphocytes was 16 times as high as that of the heavy lymphocytes. In controls, the recombined light and heavy lymphocytes showed the same reactivity as the unseparated cell suspension. Furthermore, the stimulatory capacity in the MLC was significantly higher in the light lymphocyte fraction than in the heavy lymphocytes. Finally, the capacity to recruit and to be recruited in the lymphocyte reaction on antigens was also highest in the light lymphocytes.The light and heavy lymphocytes showed a similar dose response curve as well as time courses in the response to all stimuli tested. Addition of purified monocytes to the heavy lymphocytes to the same level as was found in the light lymphocyte fraction did not restore the level of reactivity to that of the light lymphocytes. The heavy and light lymphocytes contained identical proportions of T (E rosettes), B (IgG‐bearing cells) and C3 receptor‐bearing lymphocytes (EAC rosettes). The two fractions had similar cytotoxic capacity in antibody‐dependent cytotoxicity.It is concluded that the reactivity differences are an intrinsic property of the heavy and light lymphocyte

ISSN:0014-2980    

DOI:10.1002/eji.1830080604

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractSpleen cells from C57BL/6 mice sensitized to the hapten (4‐hydroxy‐3‐nitrophenyl)acetyl (NP) were hybridized with myeloma cells, and a variety of hybrid cell lines was isolated which secreted homogeneous anti‐NP antibodies. The antibodies were purified by affinity chromatography and their chain composition, affinity and fine specificity were determined. All antibodies recovered from the primary immune response carried λ light and μ or γ1heavy chains. Their variable portions were nonidentical but similar in terms of hapten‐binding specificity with a higher affinity for the cross‐reacting haptens (4‐hydroxy‐3,5‐dinitro‐phenyl)acetyl (NNP) and (4‐hydroxy‐5‐iodo‐3‐nitro‐phenyl)acetyl (NIP) than for the homologous hapten NP. This heteroclitic property as well as the presence of λ, μ and γ1chains are characteristic for primary anti‐NP sera of C57BL/6 mice.In contrast, four families of anti‐NP antibodies, each with a characteristic fine specificity pattern, were found among the hybrid cell antibodies derived from the hyperimmune anti‐NP response. The antibodies of one of these families were related to the antibodies recovered from the primary immune response in that they were heteroclitic and carried λ light chains. All members of the other groups expressedkchains and were nonheteroclitic.The finding of well‐defined antibody families in this system and the isolation of their members enable us to approach the problem of V ge

ISSN:0014-2980    

DOI:10.1002/eji.1830080605

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractThe phenomenon of natural cytotoxicity or spontaneous cell‐mediated cytotoxicity (SCMC) was investigated in guinea pigs and compared with two otherin vitrocytotoxicity reactions: mitogen‐induced cellular cytotoxicity (MICC) and antibody‐dependent cellular cytotoxicity (ADCC). The same xenogeneic target cells were employed in all three cytotoxicity assays.Organ distribution studies revealed that SCMC effector cell activity was present in spleen and peripheral blood but not in thymocytes. Bone marrow cells possessed low levels of SCMC effector cell activity. The organ distribution of effector cell activities for MICC and ADCC paralleled that for SCMC. Studies of the cell surface characteristics of the SCMC effector cell revealed that spleen cells nonadherent to antigen‐antibody but not to antigen‐F(ab')2antibody‐coated surfaces possessed markedly reduced SCMC effector cell activity. In addition, spleen cells depleted of Fc receptor‐bearing cells by EA rosetting also possessed diminished SCMC effector cell activity, while cell populations enriched in Fc receptorbearing cells by EA resetting possessed enhanced SCMC effector cell activity. These fractionation techniques had similar effects on MICC and ADCC effector cell activity. Depletion of adherent spleen cells including macrophages by nylon wool column passage resulted in a population of cells with enhanced SCMC, MICC, and ADCC effector cell activity.Thus, in guinea pig spleen the effector cells mediating SCMC were shown to belong to a population of nonadherent Fc receptor‐bearing lymphocytes possessing several cytotoxic capabilities including the potential of mediatin

ISSN:0014-2980    

DOI:10.1002/eji.1830080606

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractAntibody responses to the penicilloyl (BPO) group, the major antigenic determinant of penicillin allergy induced in C3H mice by penicilloylated bovine gamma globulin in complete Freund's adjuvant, were reduced or abolished by various amino acid polymers and copolymers of different composition and size carrying BPO groups. Tolerogenic treatment was effective before or after primary immunization and also during anamnestic responses. The unresponsive state was of long duration and persisted even after several booster injections when efficient tolerogens were used. Among the most promising tolerogens are fully penicilloylated oligolysines with a molecular weight below 10 000.

ISSN:0014-2980    

DOI:10.1002/eji.1830080607

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractA specific tolerant state to the major antigenic determinant of penicillin allergy, the penicilloyl group, was induced in C3H mice primarily immunized with penicilloylated bovine gamma globulin in complete Freund's adjuvant. Tolerance was obtained by intraperitoneal administration of either of two penicilloyl‐bearing dextrans of molecular weight 2 × 106. One conjugate contained penicilloyl groups stably bound via a 1,6‐diaminohexane spacer, the other bore the penicilloyl groups directly bound to the hydroxyl groups of the carrier. These directly bound penicilloyl groups undergo hydrolytic cleavage within 3 days under physiological conditions in neutral aqueous solution. Model experiments showed that the rapid cleavage into carrier and haptenic derivatives also applies to penicilloylated dextran in receptor‐bound and particulate form, as may be expected from the highly hydrophilic character of the conjugate. The stable conjugate at 1 mg and the cleavable conjugate at 4 mg doses induced comparable tolerance lasting for at least 8–12 weeks.For hapten‐dextran tolerance these findings make very unlikely any mechanism requiring the continuous presence of unmodified tolerogen on the membrane or in the interior of tolerant cells, and imply second‐stage processes to explain the long duration of unresponsiveness. They also show that cleavable penicilloyl tolerogens may be considered for prospective

ISSN:0014-2980    

DOI:10.1002/eji.1830080608

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractThe antibody responses to the random linear terpolymer poly(LLyu54,LLys36,LAla10), and its 2,4 dinitrophenyl conjugate, DNP‐GLA, were analyzed. Dominant immune response genes (Ir genes) mapping to the I region of the murine major histocompatibility complex control the magnitude of the anti‐GLA and DNP‐GLA antibody responses. Mice of the H‐2f haplotype were found to be high responders. These animals produce significantly higher titers of anti‐GLA antibody to GLA than intermediate H‐2‐congenic responder mice of the H‐2b,a,d,k,s,u,v or zhaplotypes. In contrast, animals with H‐2 haplotypes j,n,p,q or r were found to be nonresponders to GLA. The relative magnitude of each strain's response to GLA was also reflected in the relative magnitude of its anti‐DNP antibody response to DNP‐GLA. High, intermediate and nonresponder mice could be further distinguished by the number of antigen‐specific plaque‐forming cells generated in the response to GLA, and in the relative amounts of IgM, IgG1and IgG2anti‐GLA antibodies produced in both primary and secondary anti‐GLA responses. Both intermediate and nonresponder strains of mice, however, could respond to GLA that was chemically coupled with an immunogenic carrier, chicken gamma globulin, to generate antigen‐specific plaque‐forming responses that were similar in magnitude to that produced by high responder strains to GLA.Isoelectric focusing studies revealed that GLA intermediate responder mice generated anti‐DNP antibody responses to DNP‐GLA of very restricted heterogeneity. H‐2‐congenic high responder animals, however, produced anti‐DNP antibody responses upon DNP‐GLA immunization that were significantly more heterogeneous than these restricted anti‐DNP‐GLA responses of intermediate responder animals. Thus, genes located within the major histocompatibility complex can influence the degree of heterogeneity of the anti‐DNP antibody response to DNP‐GLA. The potential mechanisms responsible for the Ir gene‐controlled differences in the magnitude or heterogeneity of the immune response

ISSN:0014-2980    

DOI:10.1002/eji.1830080609

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractWe have studied the ability of various antisera to induce resistance to complement‐dependent lysis (CdL) (lysostripping) of surface antigens of B and T lymphoma cells. Alloantisera, xenoantisera, as well as anti‐Rauscher‐leukemia virus (RLV) antisera, were used. Whereas all antisera could induce resistance to CdL mediated by the same serum that served for lysostripping (autolysostrip), only some of the tested antisera could induce resistance to CdL by other antisera (co‐lysostrip). In some combinations co‐lysostrip was unidirectional,i.e.in a pair of antisera, one induced autolysostrip as well as co‐lysostrip, whereas the other antiserum induced autolysostrip only. In other combinations co‐lysostrip was reciprocal.These investigations do not support the possibility that viral components and alloantigenic determinants are associated on mouse l

ISSN:0014-2980    

DOI:10.1002/eji.1830080610

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY

摘要:

AbstractAnti‐sheep red cell, anti‐dinitrophenyl, anti‐phosphorylcholine antibody responses have been followed in isogenic frogs of the genusXenopus. Isoelectric focusing antibody patterns show a high degree of overlap for all antigens studied, and a heterogeneity that is lower than in mammals for the same antigens. Inheritance of antibody isoelectric focusing spectrotypes was demonstrated for sheep red cells and dinitrophenyl in two clones of isogenic animals.Outbred frogs show a higher frequency of spectrotype sharing than outbred mammals. It is therefore suggested that antibody diversity is lower in frogs than in ma

ISSN:0014-2980    

DOI:10.1002/eji.1830080611

出版商:WILEY‐VCH Verlag GmbH    

年代:1978

数据来源: WILEY