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Biomedical subjects

K Eichmann

Publications and source records attributed to K Eichmann.

At least 145 records · Page 8Linked to original sources
PubMed1979

Establishment of a human lymphoblastoid cell line with specific antibody production against group A streptococcal carbohydrate.

A human lymphoblastoid cell line, secreting specific antibody against Group A carbohydrate (A-CHO) was established by pre-selection of antigen binding normal human lymphocytes, followed by Epsetin Barr virus (EBV) induced immortalization. Culture supernatants were assayed for anti A-CHO antibodies by radioimmunoassay, N-acetyl-glucosamine-coupled T4-phage plaque inhibition tests and passive hemagglutination. As a rule, the supernatants contained about 10 micrograms/ml anti-A-CHO antibodies of the IgM-kappa type. The antibody was fractionated and partially purified on an N-acetyl glucosamine Sepharose 4B column with a recovery of about 3 micrograms/ml of supernatant.

Antibody Formation↗
PubMed1978

Recognition of idiotypes in lymphocyte interactions. I. Idiotypic selectivity in the cooperation between T and B lymphocytes.

Idiotypic restrictions are demonstrated in vitro for the cooperation between T and B lymphocytes with specificity for Group A streptococcal carbohydrate. T helper cells which have been primed in vivo with anti-idiotypic antibodies to the A5A idiotype and which are therefore essentially A5A idiotype-positive, cooperate only with A5A idiotype-positive B cells, even when mixtures of A5A idiotype-positive and A5A idiotype-negative B cells are present. Essentially A5A idiotype-negative T helper cells that have been primed in vivo with Group A streptococcal vaccine after in vivo suppression with anti-A5A idiotypic antibody are unable to cooperate with B cells which have been primed with anti-A5A idiotype antibody and which are therefore essentially A5A idiotype-positive. Mixtures of A5A idiotype-negative and A5A idiotype-positive T cells cooperate with both A5A idiotype-negative and A5A idiotype-positive B cells. Idiotypic restrictions could not be demonstrated for T and B cells recognizing carrier and hapten determinants, respectively, in experiments in which the cooperation of genetically VH-identical T and B cells was compared to the cooperation of genetically VH-different T and B cells. The data are discussed with respect to various models for the communication between T and B cells. It is proposed that for successful T-B cooperation, ordinarily two types of T helper cells are required, one recognizing the antigen and the other recognizing the idiotype of the B cell.

Animals↗
PubMed1978

Recognition of idiotypes in lymphocyte interactions. II. Antigen-independent cooperation between T and B lymphocytes that possess similar and complementary idiotypes.

Antigen-independent cooperation between T and B lymphocytes is demonstrated in vitro in two different experimental protocols: (a) B cells from A/J mice immunized in vivo either with Group A streptococcal vaccine (Strep A) or with the IgG1 fraction of guinea pig anti-idiotypic antibody to the A5A idiotype, mature into plaque-forming cells (PFC) with specificity for Group A streptococcal carbohydrate (A-CHO) during a 4-day culture together with T cells from A/J mice immunized in vivo with A5A idiotypic antibody. (b) B cells from A/J mice immunized in vivo with Strep.A generate PFC specific for A-CHO when cultured in the presence of small concentrations of anti-A5A idiotypic antibody and of T cells primed with Strep.A. In both cases, antigen-independent cooperation is idiotypically selective, such that only those B cells respond that secrete antibody with the A5A idiotype. The data are interpreted to suggest that, in addition to antigen-specific helper cells, idiotype-specific may participate in antibody responses, and that the latter type of help may be responsible for the idiotypic selectivity in T-B cooperation observed previously. Furthermore, idiotype-specific cooperation may be a means to generate and maintain B cell diversity during the evolution and ontogeny of the immune system.

Animals↗
PubMed1978

Genetics of the idiotype of strain AKR antibodies to group A streptococcal carbohydrate; further evidence for a low degree of homology in the VH chromosomal region.

A new VH gene is described which governs the expression of idiotypes associated with the antibody response of strain AKR mice to Group A streptococcal carbohydrate (A-CHO). This VH gene, termed ACHd, is identified using guinea pig antisera to a pool of strain AKR antibodies to A-CHO. The genetic polymorphism is revealed by quantitative differences in idiotype expression between different inbred strains. In recombinant inbred strains linkage to the Ig-1d allotype allele of strain AKR is demonstrated. In a putative recombinant strain it appears that ACHd maps at a locus different from that of A5A+, another VH gene controlling idiotypes of anti-A-CHO antibodies. This represents a further example of pseudoallelism between related VH genes and lack of homology in the VH chromosomal region. Expression of the ACHd gene was independent of the Ly-2, 3 locus which is associated with kappa chain variants.

Animals↗
PubMed1977

Absolute frequencies of lipopolysaccharide-reactive B cells producing A5A idiotype in unprimed, streptococcal A carbohydrate-primed, anti-A5A idiotype-sensitized and anti-A5A idiotype-suppressed A/J mice.

The absolute frequencies of B cells-producing A5A idiotype have been determined in vitro by limiting dilution analysis in a culture system in which every LPS-reactive B cell grows into a clone of IgM-secreting cells. Spleen cells from normal A/J mice contain 1 A5A-idiotype-producing B-cell precursor in 2.5 X 10(3) LPS-reactive B cells. Approximately a 10-20-fold increase in frequencies of precursor cells from antigen priming with Strep A-CHO (1 in 2.8 X 10(2)) or from sensitization with IgG1 anti-A5A idiotype (1 in 1.3 X 10(2)). Injection of IgG2 anti-A5A idiotype which has been shown to suppress A5A idiotype in vivo results in only a marginal and maybe insignificant decrease in precursor frequencies (1 in 6.7 X 10(3)). On the other hand, priming does not result in a detectable qualitative difference in the specific precursor cells, since each clone of B cells secretes 30 ng of A5A-bearing Ig within 8 days of culture, regardless of being unprimed or primed. Nearly half of all A5A idiotype-producing clones, both from unprimed as well as from primed mice, show antigen specificity in binding A-CHO. Priming by antigen, therefore, also results in a 10-fold increase in the frequency of idiotype positive B cells without antigen specificity. This result is a prediction of the network hypothesis.

Animals↗
PubMed1977

On the structure of the T-cell receptor for antigen.

Antigen-binding receptors of T lymphocytes were analyzed in two different ways. First, the idiotypic properties of T helper cells are studied using anti-idiotypic antisera prepared against isolated antibodies specific for A-CHO. These anti-idiotypic antisera are defined by immunogenetic and immunochemical means with respect to their reactivity with heavy- or light-chain-associated idiotypic determinants. Second, antigen-binding receptors are isolated from enriched T-and B-lymphocyte preparations and compared with respect to their reactivity with antigen and with class- or allotype-specific anti-Ig antisera. The results provide an incomplete picture of the T-cell receptor which shares with antibodies the variable region of the heavy chain but probably no other variable or constant portion.

Animals↗
PubMed1976

Genetics of the idotype of BALB/c myeloma S117: multiple chromosomal loci for Vh genes encoding specificity for group A streptococcal carbohydrate.

A small proportion of the antibodies to Group A streptococcal carbohydrate (A-CHO) elicited in BALB/c mice by immunization with Group A streptococci, has idiotypic determinants in common with the BALB/c myeloma protein S117 which has specificity for N-acetyl-glucosamine, the major antigenic determinant of A-CHO. The expression of these idiotypic determinants is under the control of a gene which is linked to the Ig-1a+ allotype locus in strain BALB/c and in other strains carrying the same Ig-1 haplotype. This gene (S117+) segregates in breeding experiments as if it were an allele to the gene A5A+ which controls the expression of the A5A idiotype in association with antibodies to A-CHO in strain A/J and which is linked to the Ig-1e allotype locus. Another possible allele, linked to the Ig-1c allotype locus, controls the expression of both S117 and A5A cross-reactive determinants (S117cr, A5Acr). The distribution of these idiotypic determinants in various lines that carry recombinant Ig-1 haplotypes suggests that the A5A and S117 loci are nonallelic and map at different positions in the Ig-1 region. The data suggest complex pseudollelic relationships between different Ig-1 haplotypes that allow the expression of the same genes in allelic and in nonallelic fashion.

Alleles↗
PubMed1976

Idiotypic analysis of lymphocytes in vitro. I. Specificity and heterogeneity of B and T lymphocytes reactive with anti-idiotypic antibody.

Guinea pig anti-idiotypic antibodies (anti-Id) of the IgG1 class, directed to an A/J antibody to Group A streptococcal carbohydrate (A-CHO), or directed to a BALB/c myeloma protein that binds the same antigen, stimulate B-precursor cells as well as T-helper cells when injected into mice of the appropriate strain. The strain-specific induction of both precursor and helper activity was detected by in vitro secondary responses of primed spleen cells to A-CHO or to 2,4,6-trinitrophenyl (TNP) upon challenge with Group A streptococcal vaccine (Strep.A) or with TNP-Strep.A, respectively. B- and T-cell populations primed with anti-Id were uniform with respect to the binding of antigen and of anti-Id. This was in contrast to cells primed with Strep.A, which were heterogenous. Taken together, B and T cells that possess the same antigen-binding specificity share idiotypic determinants, reveal the same idiotypic polymorphism, and may display similar degrees of heterogeneity with respect to the binding of antigen and anti-Id. Since the anti-Id used in this study detect Id determinants associated with the heavy chain of the variable region of mouse antibodies, the data suggest that this region of the immunoglobulin molecule is shared between T- and B-cell antigen receptors.

Acetylglucosamine↗
PubMed1976

Idiotypic analysis of lymphocytes in vitro. II. Genetic control of T-helper cell responsiveness to anti-idiotypic antibody.

When the IgG1 fraction of anti-idiotypic antibodies raised in guinea pigs is injected into mice, sensitization of idiotypic T and B lymphocytes occurs (1-3). In the present study we analyze the genetic requirements for T-helper cell sensitization by anti-idiotypic antibody. This was done by measuring, in a suitable panel of mouse strains, helper cell responsiveness to two anti-idiotypic reagents which recognize distinct, strain-specific idiotypes, namely the A5A and the S117 marker. Whenever helper cell sensitization by anti-idiotypic antibody was successful, helper function could be specifically inhibited by the same and only the same anti-idiotype. This indicates that helper cells induced by anti-idiotypic antibody express idiotypic determinants on their receptors for antigen. Helper cell sensitization by anti-idiotypic antibody was found in all strains expressing the corresponding or a cross-reactive idiotype at the immunoglobulin level. Idiotype-negative strains were always unresponsive to anti-idiotypic stimulation. In addition, responsiveness did not depend on the H-2 haplotype. Since the A5A and the S117 idiotype are markers for V genes in the heavy-chain linkage group, the present results support the view that the same genes in the Ig-1 complex code for variable portions of immunoglobulins and T-helper cell receptors.

Animals↗
PubMed1976

Expression of Ia determinants on immunocompetent cells.

The expression of Ia (immune response region-associated) antigens on the surface of lymphocyte subpopulations with defined immunological function has been investigated by negative selection of subpopulations with anti-Ia sera and complement. Ia determinants were found on both unprimed (IgM) and on primed (IgG) antibody-forming precursor cells. No Ia antigens were detected on the surface of helper T cells. In contrast, suppressor T cells were sensitive to treatment with anti-Ia sera and complement demonstrating the presence of Ia determinants on this T cell subpopulation.

Animals↗
PubMed1976

Structural studies on induced antibodies with defined idiotypic specificities. III. N-terminal amino acid sequence of the heavy and light chains of mouse anti-streptococcal antibodies--A5A, S8, and S117.

The murine VH genetic map consists of two different subloci of VH genes. Seven idiotypes have been allocated to these two different subloci, one of which contains genes coding for the A5A idiotype, while the second contains the genes encoding for six other idiotypic markers. Previous studies from this laboratory have shown that anti-Ars antibodies are best classified in the murine VHII subgroup. Studies from other laboratories indicate that the J558 idiotype could be classified in a similar fashion. The sequence of the T15 myeloma protein VH region is most characteristic of the murine VHIII subgroup. These studies were undertaken in order to study the VH subgroup of two additional murine VH markers. Since one of these markers has been allocated to a separate sublocus, comparisons can be made for the first time between the "framework" residues (VH subgroup) and the murine genetic map. The data indicate that within a single presently defined sublocus proteins exist which contain remarkably different "framework" residues.

Amino Acid Sequence↗
PubMed1975

Idiotype suppression. II. Amplification of a suppressor T cell with anti-idiotypic activity.

Guinea pig IgG2 anti-idiotypic antibody (aId2) against the strain A/J antibody A5A has a suppressive effect on the expression of the A5A idiotype in adult A/J mice immunized with Group A streptococci. High doses of aId2 cause an immediate but transient suppression, whereas low doses of aId2 result in a delayed but chronic suppression which lasted for more than 1 year without any indication of recovery. Chronic suppression is transferred by as few as 10(5) spleen cells, but an interval of 6 weeks after transfer is required for completion of suppression. The suppressive capacity of aId2-induced suppressor cells was virtually inexhaustable in 4 consecutive transfers spaced at 3 month intervals. The suppressor cell is a T cell which adheres to histamine-rabbit serum albumin-Sepharose 2B columns.

Animals↗
PubMed1975

Induction of T and B cell immunity by anti-idiotypic antibody.

A small dose of the IgG1 fraction of anti-idiotypic antibody (aId1) raised in guinea pigs against a strain A/J antibody specific for streptococcal Group A carbohydrate sensitizes A/J mice against Group A streptococci. This is opposed to the previously established suppressive function of anti-idiotypic antibody of the IgG2 class (aId2). Correspondingly, aId1 but not aId2 is eliminated from the circulation in the way typical of an immunogenic molecule. However, the stimulatory component in the IgG1 fraction is not necessarily itself IgG1 antibody. Sensitization occurs in both B and helper T lymphocytes and is specific for Group A streptococci. In the B cell compartment sensitization is restricted to precursor cells expressing the idiotype. The concomitant activation of T helper cells therefore suggests that these cells make use of receptors with a similar or identical idiotype. Efficient sensitization by aId1 of both T and B cells is also demonstrated in strain C57L/J mice which upon immunization with Group A streptococci express a partially cross-reacting idiotype as a minor component. When such animals were primed with aId1, essentially all of the anti-carbohydrate antibody carried the partially cross-reacting idiotype.

Animals↗