scholarly journals Antibody response of C3H in equilibrium (CKB X CWB)F1 tetraparental mice to poly-L(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys immunization.

1976 ◽  
Vol 144 (1) ◽  
pp. 123-144 ◽  
Author(s):  
K B Bechtol ◽  
H O McDevitt
Keyword(s):  
B Cells ◽  
Antibody Response ◽  
High Responder ◽  
Low Responders ◽  
First Case ◽  
Low Responder ◽  
Specific Stimulation ◽  
Stimulation Of

To test whether the antigen-specific stimulation of low responder-genotype B cells in tetraparental mice is due to a histoincompatibility reaction (allogeneic effect) against these B cells, tetraparental mice were constructed (a) between an Ir-1A low responder to the antigen poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys. [(T,G)-A--L] and an Ir-1A F1 high responder and (b) between two histoincompatible Ir-lA low responders. In the first case the F1 high responder embryo shares the whole of the H-2 complex, including Ir, with the low responder embryo.

scholarly journals GENETIC CONTROL OF THE ANTIBODY RESPONSE TO POLY-L(TYR,GLU)-POLY-D,L-ALA--POLY-L-LYS IN C3H↔CWB TETRAPARENTAL MICE

1974 ◽  
Vol 140 (6) ◽  
pp. 1660-1675 ◽  
Author(s):  
Kathleen B. Bechtol ◽  
John H. Freed ◽  
Leonard A. Herzenberg ◽  
Hugh O. McDevitt
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Antibody Response ◽  
Genetic Control ◽  
Binding Capacity ◽  
High Responder ◽  
Total Serum ◽  
Antigen Binding ◽  
Low Responder

In order to further delineate the mechanisms underlying genetic unresponsiveness, tetraparental mice were constructed from immune response-1A gene high responder and low responder parental genotypes, then were immunized with poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys ((T,G)-A--L). An analysis of the total serum allotype mixture and of the antigen-binding capacity of the separated allotypes demonstrated that in the milieu of a tetraparental mouse, both high and low responder B cells could be stimulated equally to produce identical high titered anti-(T,G)-A--L responses. Furthermore, these studies show that effective stimulation could occur across a histocompatibility disparity.

scholarly journals ANTIGEN-SPECIFIC THYMUS CELL FACTORS IN THE GENETIC CONTROL OF THE IMMUNE RESPONSE TO POLY-(TYROSYL, GLUTAMYL)-POLY-D, L-ALANYL--POLY-LYSYL

1974 ◽  
Vol 140 (2) ◽  
pp. 301-312 ◽  
Author(s):  
M. J. Taussig ◽  
Edna Mozes ◽  
Ronit Isac
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antibody Response ◽  
Genetic Control ◽  
Bone Marrow Cells ◽  
High Responder ◽  
Low Responder

The genetic control of the antibody response to a synthetic polypeptide antigen designated poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(T, G)-A--L] has been studied in congenic high responder C3H.SW (H-2b) and low responder C3H/HeJ (H-2k) strains of mice. This response is controlled by the Ir-1 gene and is H-2 linked. The method employed was to study the ability of specifically primed or "educated" T cells of each strain to produce cooperative factors for (T, G)-A--L in vitro. Such factors have been shown to be capable of replacing the requirement for T cells in the thymus-dependent antibody response to (T, G)-A--L in vivo. The T-cell factors produced were tested for their ability to cooperate with B cells of either high or low responder origin by transfer together with bone marrow cells and (T, G)-A--L into heavily irradiated, syngeneic (for bone marrow donor) recipients. Direct anti-(T, G)-A--L plaque-forming cells were measured later in the spleens of the recipients. The results showed that (a) educated T cells of both high and low responder origin produced active cooperative factors to (T, G)-A--L, and no differences between the strains in respect to production of T-cell factors could be demonstrated; and (b) such factors, whether of high or low responder origin, cooperated efficiently with B cells of high responder origin only, and hardly at all with B cells of low responder origin. The conclusion was drawn that the cellular difference between the two strains lies in the responsiveness of their B cells to specific signals or stimuli received from T cells. As far as could be discerned by the methods used, no T-cell defect existed in low responder mice and the expression of the controlling Ir-1 gene was solely at the level of the B cells in this case.

scholarly journals COMPARATIVE ANALYSIS OF ANTIGEN-BINDING T CELLS IN GENETIC HIGH AND LOW RESPONDER MICE

1974 ◽  
Vol 140 (5) ◽  
pp. 1180-1188 ◽  
Author(s):  
Günter J. Hämmerling ◽  
Hugh O. McDevitt
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Comparative Analysis ◽  
Antibody Response ◽  
Mouse Serum ◽  
Antigen Binding ◽  
Albumin Binding ◽  
Low Responders ◽  
Low Responder ◽  
High Responders

[125I](T,G)-A--L-binding T cells have been studied in mice whose ability to mount an immune response to (T,G)-A--L is under control of the H-2-linked Ir-1A gene. Nonimmunized high and low responder mice have approximately the same frequency of T-ABC. Following immunization, T-ABC proliferated only in high responders, but not in low responders, indicating expression of Ir-1A in T cells. When, for comparison, [125I]arsanyl-mouse serum albumin binding B and T cells were investigated in mice whose antibody response to the hapten arsanyl is controlled by an allotype-linked Ir gene, it was found that following immunization the number of B-ABC increased only in high responders. In contrast, T-ABC proliferated to the same extent in both high and low responders, suggesting exclusive expression of the allotype-linked Ir gene in the B-cell line. Preliminary studies indicate that anti-Ia sera inhibit neither B-ABC nor T-ABC.

scholarly journals Genetic control of immune response to myoglobin. Ir gene function in genetic restriction between T and B lymphocytes.

1982 ◽  
Vol 156 (5) ◽  
pp. 1486-1501 ◽  
Author(s):  
Y Kohno ◽  
J A Berzofsky
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
High Responder ◽  
Gene Control ◽  
Gene Defect ◽  
Genetic Restriction ◽  
Low Responder

We studied the genetic restrictions on the interaction between T cells, B cells, and antigen-presenting cells (APC) involved in the H-2-linked Ir gene control of the in vitro secondary antibody response to sperm whale myoglobin (Mb) in mice. The B cells in this study were specific for Mb itself, rather than for a hapten unrelated to the Ir gene control, as in many previous studies. Low responder mice immunized in vivo with Mb bound to an immunogenic carrier, fowl gamma globulin (F gamma G), produced B cells competent to secrete anti-Mb antibodies in vitro if they received F gamma G-specific T cell help. However, (high-responder X low responder) F1 T cells from Mb-immune mice did not help these primed low responder (H-2k or H-2b) B cells in vitro, even in the presence of various numbers of F1 APC that were demonstrated to be component to reconstitute the response of spleen cells depleted by APC. Similar results were obtained with B6 leads to B6D2F1 radiation bone marrow chimeras. Genotypic low responder (H-2b) T cells from these mice helped Mb-primed B6D2F1B cells plus APC, but did not help syngeneic chimeric H-2b B cells, even in the presence of F1 APC. In contrast, we could not detect any Ir restriction on APC function during these in vitro secondary responses. Moreover, in the preceding paper, we found that low responder mice neonatally tolerized to higher responder H-2 had competent Mb-specific helper T cells capable of helping high responder but not low responder B cells and APC. Therefore, although function Mb-specific T cells and B cells both exist in low responder mice, the Ir gene defect is a manifestation of the failure of syngeneic collaboration between these two cell types. This genetic restriction on the interaction between T cells and B cells is consistent with the additional new finding that Lyb-5-negative B cells are a major participant in ths vitro secondary response because it is this Lyb-5-negative subpopulation of B cells that have recently been shown to require genetically restricted help. The Ir gene defect behaves operationally as a failure of low responder B cells to receive help from any source of Mb-specific T cells either high responder, low responder, or F1. The possible additional role of T cell-APC interactions, either during primary immunization in vivo or in the secondary culture is discussed.

scholarly journals The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody

1978 ◽  
Vol 147 (6) ◽  
pp. 1849-1853 ◽  
Author(s):  
CM Warner ◽  
TJ Berntson ◽  
L Eakley ◽  
JL McIvor ◽  
RC Newton
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Glutamic Acid ◽  
Gamma Globulin ◽  
High Responder ◽  
Gene Control ◽  
Low Responder ◽  
Bone Marrow Chimeras

The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder × high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.

scholarly journals Genetic control of the immune response to staphylococcal nuclease. IV. H-2-linked control of the relative proportions of antibodies produced to different determinants of native nuclease.

1977 ◽  
Vol 145 (1) ◽  
pp. 123-135 ◽  
Author(s):  
J A Berzofsky ◽  
A N Schechter ◽  
G M Shearer ◽  
D H Sachs
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Antibody Response ◽  
Binding Capacity ◽  
Staphylococcal Nuclease ◽  
Gene Control ◽  
Low Responder ◽  
Selection Of ◽  
Ir Genes

The relative proportions of antibodies of different specificities within antisera raised to native staphylococcal nuclease have been studied in several strains of mice in which the antibody response has been shown to be under H-2-linked Ir-gene control. A method was developed in which binding to different radiolabeled fragments of nuclease was titrated against increasing fragment concentration until the binding capacity of the antiserum for that fragment was saturated. In comparing the low responder (H-2b) strain C57BL/10 with its congenic high responder counterpart B10.A (H-2a), it was found that the two strains made markedly and reproducibly different proportions of antibodies to different determinants on native nuclease. Since these two strains differ only at H-2, and therefore have identical immunoglobulin structural gene repertoires, we conclude that H-2-linked Ir genes can control the response to different determinants on the same antigen molecule independently of one another. This result suggests a possible role of H-2-linked genes in the selection of specific B cells.

scholarly journals Genetic control of the immune response to staphylococcal nuclease. III. Time-course and correlation between the response to native nuclease and the response to its polypeptide fragments.

1977 ◽  
Vol 145 (1) ◽  
pp. 111-122 ◽  
Author(s):  
J A Berzofsky ◽  
A N Schechter ◽  
G M Shearer ◽  
D H Sachs
Keyword(s):  
Antibody Response ◽  
Time Course ◽  
Staphylococcal Nuclease ◽  
High Responder ◽  
Gene Control ◽  
Linked Gene ◽  
Low Responder ◽  
The Common ◽  
Antibody Levels ◽  
Or Genes

The progression of the Ir gene-controlled antibody response to staphylococcal nuclease in mice with repeated immunizations has been examined. H-2-linked control of the response to a single immunization with 100 mug of nuclease in complete Freund's adjuvant was confirmed. However, among strains of the high responder H-2a haplotype, the response of the A/J mice was about 10-fold higher than that of the B10.A, indicating additional non-H-2-linked control. In addition, the low responder C57BL/10 (H-2b) strain produced antibody levels as high as or higher than those of the congenic high responder B10.A (H-2a) strain when both strains were repeatedly immunized, indicating complexity even in the H-2-linked control of the response to this small monomeric protein. Polypeptide fragments of nuclease were also studied as immunogens. The antibody response to one fragment (residues 99-149) was found to follow the same pattern among five strains tested as that to whole nuclease. However, in this case the C57BL/10 was found to be a nonresponder rather than a low responder, failing to develop a response despite repeated immunizations. In contrast, the C57BL/10 showed a low but significant response to another fragment (residues 1-126) of nuclease. These results suggest that the apparent H-2-linked control of the response to whole nuclease is a reflection of the ability to recognize a determinant(s) in the region from residues 99 to 149, and that the eventual response of the C57BL/10 strain after hyperimmunization reflects the recognition of other determinants. If these observations reflect the common recognition of a determinant on native nuclease and on a random-conformation fragment, they have implications about the conformational specificity of the receptors, or the flexibility of the determinants, involved in H-2-linked Ir-gene control. In addition, evidence is presented for a possible second H-2-linked gene (or genes) controlling the response to other determinants of nuclease expressed on the polypeptide fragments.

Nematospiroides dubius: the course of primary, secondary and tertiary infections in high and low responder Biozzi mice

Parasitology ◽  
1981 ◽  
Vol 82 (2) ◽  
pp. 311-318 ◽  
Author(s):  
D. C. Jenkins ◽  
Trudi S. Carrington
Keyword(s):  
Primary Infection ◽  
Egg Production ◽  
Essential Role ◽  
Antibody Responses ◽  
High Responder ◽  
Macrophage Activity ◽  
Low Responders ◽  
Wide Range ◽  
Low Responder ◽  
Nematospiroides Dubius

SUMMARYBiozzi mice of Selections 1 and 3, each exhibiting either high- or low- antibody responses to a wide range of antigens, were exposed to primary, secondary and tertiary infections of the nematode, Nematospiroides dubius. The course of these infections was followed by monitoring egg output and by examination of the worm burdens on the 14th day after each exposure to the parasite. When exposed to a primary infection, high and low responders were equally susceptible to the parasite, and the egg production of the infections was similar in all groups. However, when the mice were exposed to a 2nd infection of N. dubius, marked differences in the susceptibility of the hosts were seen. The high-responder mice of both Selections 1 and 3 were significantly more resistant to infection, far less adult worms being found in these. Resistance to a 3rd and final infection of the parasite was amplified appreciably in all groups but, again, the high-responder mice were significantly more resistant than the low responders. These results imply that host antibodies play an essential role in immunity to this parasite and that resistance cannot be attributed solely to non-specific macrophage activity or cell-mediated immune reactions, since the latter are equivalent in high and low lines and the macrophages of the Ab/L line of Selection 1 are hyperactive.

scholarly journals The role of H-2 linked genes in helper T-cell function. IV. Importance of T-cell genotype and host environment in I-region and Ir gene expression.

1978 ◽  
Vol 148 (6) ◽  
pp. 1510-1522 ◽  
Author(s):  
J W Kappler ◽  
P Marrack
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
High Responder ◽  
Helper T Cells ◽  
Helper T Cell ◽  
Region Gene ◽  
Host Environment ◽  
Low Responder

We have studied the properties of helper T cells specific for sheep erythrocytes (SRBC), keyhole limpet hemocyanin (KLH), or poly-L-(Tyr,Glu)-poly-DL-Ala-poly-L-Lys [(T,G)-A--L]. These T cells differentiated and were primed in vivo in irradiation chimeras constructed of various combinations of F1 and parental bone marrow donors and irradiated recipients. Primed T cells were then tested for helper activity in the in vitro response of B cells and macrophages (Mphi) of parental or F1 origin to the hapten trinitrophenol coupled to the priming antigen. When testing either SRBC or KLH-specific T cells of parental H-2 type which had differentiated in F1 hosts, we found that they cooperated equally well with B cells and Mphi of either parental H-2 type. On the other hand, when testing F1 T cells which had differentiated in parental hosts, we found that they cooperated well only with B cells and Mphi which had the K-IA region type of the parental host. In similar experiments we found that (T,G)-A--L-specific T cells of low responder H-2 type which had differentiated in (high responder X low responder) F1 hosts induced high responses in high responder B cells and Mphi (T,G)-A--L-specific F1 T cells which differentiated in high responder but not those which differentiated in low responder hosts induced high responses in high responder B cells and Mphi. Low responder B cells and Mphi yielded low responses in all cases regardless of the source of (T,G)-A--L-specific T cells with what they were tested. Our results support the conclusion that I-region and Ir genes function via their expression in B cells and Mphi and in the host environment during helper T-cell differentiation, but not, at least under the conditions of these experiments, via their expression in the helper T cell itself. These findings place constraints upon models which attempt to explain the apparent dual recognition of antigen and I-region gene products by helper T cells.

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