scholarly journals INHERITANCE OF ANTIBODY SPECIFICITY

1974 ◽  
Vol 140 (6) ◽  
pp. 1498-1510 ◽  
Author(s):  
Thereza Imanishi ◽  
O. Mäkelä
Keyword(s):  
Primary Response ◽  
Mouse Strains ◽  
Antibody Specificity ◽  
Monogenic Inheritance ◽  
Fine Specificity ◽  
Homozygous Mouse ◽  
Relative Affinity ◽  
V Genes

Our data suggest that fine specificity of antihapten antibodies is a useful Mendelian marker of variable (V) genes. We found that some mouse strains (e.g., C57/BL6) consistently produced heteroclitic anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies (relative affinity for related (4-hydroxy-5-iodo-3-nitrophenyl)acetyl and (4-hydroxy-3.5-dinitrophenyl)acetyl was always >2) while other strains (e.g., CBA) produced "conventional" anti-NP antibodies (relative affinities were consistently <1). 48 (CBA x C57BL/6)F1 mice were studied and most of them had heteroclitic anti-NP antibodies. They were backcrossed to the recessive CBA parent, and 87 backcross animals were similarly tested. Those heterozygous for the C57BL/6 heavy (H)-chain allotype were similar to the C57BL/6 and the F1 mice while mice homozygous for the CBA allotype were indistinguishable from the CBA. Such monogenic inheritance was observed only in the primary response. Predominance of allotype-linked genes in the control of the fine specificity characteristics was confirmed by immunizing selected homozygous mouse strains. These mice contained various mixtures of genes from C57BL, BALB/c, and other strains. Specificity of their anti-NP was exclusively determined by genes linked to the H-chain allotype, no influence could be attributed to other genes including the H-2-linked genes.

scholarly journals Inheritance of antibody specificity. II. Anti-(4-hydroxy-5-bromo-3-nitrophenyl) acetyl in the mouse.

1975 ◽  
Vol 141 (4) ◽  
pp. 840-854 ◽  
Author(s):  
T Imanishi ◽  
O Makela
Keyword(s):  
Recombinant Inbred ◽  
Inbred Strains ◽  
The Other ◽  
Antibody Specificity ◽  
Linked Gene ◽  
Fine Specificity ◽  
The Third ◽  
Relative Affinity ◽  
B Mice ◽  
Recombinant Mice

Mice of 17 inbred strains produced anti-(4-hydroxy-5-bromo-3-nitrophenyl)-acetyl (NBrP) of three different fine specificity types. Anti-NBrP antibodies of all allotype b mice (five strains tested) had a high relative affinity for (4-hydroxy-3.5-dinitrophenyl) acetyl (NNP) but low for (4-hydroxy-5-cloro-3-nitrophenyl) acetyl (NCP). Another category was characterized by high relative affinity for NCP but low for NNP. This category included most of the tested strains. The third category (CBA and C3H strains) had an intermediate fine specificity. Associated with fine specificity characteristics were anti-NBrP titers, mice of allotype b had lower titers than the other mice. Studies of congenic, recombinant inbred, F1 and backcross mice showed that both fine specificity and the magnitude of the anti-NBrP response of tbalb/C MICE WERE CONTROLLED BY AN ALLOTYPE-LINKED GENE. This gene was dominant over the C57BL/6 ALLELE. Lack of recombinant mice in the backcross generatioterns on the other suggest close linkage between the two genes.

scholarly journals Inheritance of antibody specificity V. Anti-2-phenyloxazolone in the mouse.

1978 ◽  
Vol 148 (6) ◽  
pp. 1644-1660 ◽  
Author(s):  
O Näkelä ◽  
M Kaartinen ◽  
J L Pelkonen ◽  
K Karjalainen
Keyword(s):  
Isoelectric Focusing ◽  
Recombinant Inbred ◽  
Inbred Strains ◽  
Recombinant Inbred Strains ◽  
Mouse Strains ◽  
Antibody Specificity ◽  
Structural Analogue ◽  
Relative Affinity ◽  
Individual Mouse ◽  
The Cross

Antibodies to hapten 2-phenyloxazolone (phOx) of all BALB/c and DBA/2 mice have the same idiotype and the same major (public) isoelectric focusing pattern whose main spectrotype is called Ox-1. Neither of these characteristics could be readily demonstrated in anti-phOx antibodies of C57BL, C3H or LP mice; these antibodies were heterogeneous, and lacked public spectrotypes. Also, a fine specificty difference could be demonstrated between anti-phOx antibodies of BALB/c and C5MBL mice; the latter have a higher relative affinity than the former for a structural analogue of phOx (2-o-iodophenyloxazolone). The three BALB/c characteristics were inherited in congenic and recombinant inbred strains as an allotype-linked block, defining a new VH marker, VHphOx. Murine anti-phOx antibodies were found to exhibit three types of conservatism: (a) Every individual mouse of strains BALB/c, DBA/2 or BAB-14 had an almost indistinguishable IEF pattern. (b) These patterns (and the cross-reactive idiotype) remained virtually unchanged during an immunization course of 70 days. (c) An identical idiotype (and in some cases IEF pattern) was present in mouse strains of five different allogroups.

scholarly journals Flexibility of the T cell repertoire. Self tolerance causes a shift of T cell receptor gene usage in response to insulin.

1990 ◽  
Vol 171 (5) ◽  
pp. 1665-1681 ◽  
Author(s):  
F Falcioni ◽  
Z Dembic ◽  
S Muller ◽  
P V Lehmann ◽  
Z A Nagy
Keyword(s):  
T Cell ◽  
Receptor Gene ◽  
Bovine Insulin ◽  
Mouse Strains ◽  
Specific Response ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Fine Specificity ◽  
Self Tolerance ◽  
Gene Usage

Bovine insulin(BI)-specific I-Ab-restricted T cell clones have been characterized for fine specificity and TCR gene usage. We have demonstrated that mouse strains carrying H-2b on three different genetic backgrounds (C57BL, BALB, and 129) rearrange and express the V beta 6 gene in a large proportion (36%) of insulin-specific clones. In these strains, the non-MHC background did not seem to influence TCR gene usage in response to BI. The V beta 6+ clones appeared to be selected by the antigen. In contrast, no V beta 6+ clones could be isolated from (B6 x DBA/2)F1 mice, where V beta 6+ (and V beta 8.1+) T cells are deleted by self tolerance to Mls-1a. Thus, although a small proportion of residual V beta 6+ cells had been demonstrated in Mls-1a mice, these cells could not be retrieved in a response that uses V beta 6 predominantly. In functional terms, therefore, the deletion of V beta 6 by self tolerance appears to be complete. Instead of V beta 6, the majority (up to 60%) of I-Ab- as well as I-Ad-restricted insulin-specific clones from the (B6 x DBA/2)F1 mice expressed V beta 8.2 and V beta 8.3. This shift of gene usage was not accompanied by any detectable change in the fine specificity pattern of response. Thus, in the insulin-specific response, the flexibility of T cell repertoire fully compensates for deletions caused by self tolerance.

scholarly journals Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Bronwen R Burton ◽  
Richard K Tennant ◽  
John Love ◽  
Richard W Titball ◽  
David C Wraith ◽  
...  
Keyword(s):  
B Cells ◽  
Serum Antibody ◽  
Primary Response ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Virus Envelope ◽  
B Cell Memory ◽  
The Hierarchical Structure ◽  
V Genes ◽  
Variant Protein

Vaccines induce memory B-cells that provide high affinity secondary antibody responses to identical antigens. Memory B-cells can also re-instigate affinity maturation, but how this happens against antigenic variants is poorly understood despite its potential impact on driving broadly protective immunity against pathogens such as Influenza and Dengue. We immunised mice sequentially with identical or variant Dengue-virus envelope proteins and analysed antibody and germinal-centre (GC) responses. Variant protein boosts induced GCs with a higher proportion of IgM+ B cells. The most variant protein re-stimulated GCs with the highest proportion of IgM+ cells with the most diverse, least mutated V-genes and with a slower but efficient serum antibody response. Recombinant antibodies from GC B-cells showed a higher affinity for the variant antigen than antibodies from a primary response, confirming a memory origin. This reveals a new process of antibody memory, that IgM memory cells with fewer mutations participate in secondary responses to variant antigens, demonstrating how the hierarchical structure of B-cell memory is used and indicating the potential and limits of cross-reactive antibody based immunity.

scholarly journals Immunological unresponsiveness to thymus-independent antigens: two fundamentally different genetic mechanisms of B-cell unresponsiveness to dextran

1977 ◽  
Vol 146 (6) ◽  
pp. 1663-1677 ◽  
Author(s):  
C Fernandez ◽  
G Moller
Keyword(s):  
B Cell ◽  
Suppressor Cells ◽  
Fluorescein Isothiocyanate ◽  
Congenic Mouse ◽  
High Responder ◽  
Mouse Strains ◽  
V Genes ◽  
Genetic Mechanisms ◽  
Congenic Mouse Strains ◽  
Cell Activator

The immune response of mice to the α-l-6 epitope of dextran (Dx) B512 was found to be under genetic control. The congenic mouse strains A, A.CA, A.SW, A.TH, and A.TL exhibited a specific defect in their response to α-l-6. Also strain CBA/N was unresponsive to α-1-6, but the mechanism of unresponsiveness was found to be different. Unresponsiveness to α-l-6 in congenic A strains was not due to suppressor cells. Although these strains failed to respond to the α-l-6 epitope, they responded strongly to the hapten Fluorescein isothiocyanate (FITC) conjugated to Dx, indicating that the Dx can function as an efficient carrier in these strains. Dx was a potent polyclonal B-cell activator in congenic A strains as well as in high responder strains. Polyclonally-activating concentrations of lipopolysaccharide (LPS) failed to induce the synthesis of anti-α- l-6 antibodies in congenic A strains, although antibodies of all other specificities studied were produced. However, in high responder strains, LPS induced the synthesis of anti-α-l-6 antibodies. It was concluded that congenic A strains do not express V genes coding for antibodies against α-l-6. In contrast, strain CBA/N failed to respond to both the α-l-6 and FITC epitope on Dx, whereas they could respond to FITC conjugated to horse erythrocytes. Dx induced a very small, if any, polyclonal antibody response in B cells from CBA/N mice or male CBA/N x DBA hybrids, whereas Dx was a very potent polyclonal B-cell activator in female hybrids. It is concluded that CBA/N mice are nonresponders to Dx or haptenated Dx, because the cell population that can respond to the polyclonal B-cell activating properties of Dx is severely depleted.

Primary response to lysozyme (HEL) and HEL-LPS in neonatal A/J mice: Presence of characteristic adult pattern of regulatory idiotype and fine specificity restriction

1989 ◽  
Vol 119 (1) ◽  
pp. 143-152 ◽  
Author(s):  
Margaret A. Keller ◽  
Mark A. Kaplan ◽  
Norma S. Kenyon ◽  
Alexander Miller ◽  
Eli E. Sercarz
Keyword(s):  
Primary Response ◽  
Fine Specificity ◽  
Adult Pattern

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

1976 ◽  
Vol 143 (4) ◽  
pp. 861-869 ◽  
Author(s):  
G J Hämmerling ◽  
S J Black ◽  
C Berek ◽  
K Eichmann ◽  
K Rajewsky
Keyword(s):  
T Helper Cell ◽  
Helper Cell ◽  
Mouse Strains ◽  
Immunoglobulin Level ◽  
T Helper ◽  
Distinct Strain ◽  
V Genes ◽  
Helper Function ◽  
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.

The same few V genes account for a majority of oxazolone antibodies in most mouse strains

1992 ◽  
Vol 29 (11) ◽  
pp. 1357-1362 ◽  
Author(s):  
Marja-Liisa Solin ◽  
Matti Kaartinen ◽  
Olli Mäkelä
Keyword(s):  
Mouse Strains ◽  
V Genes

Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

1995 ◽  
Vol 53 ◽  
pp. 970-971
Author(s):  
L. Vacca-Galloway ◽  
Y.Q. Zhang ◽  
P. Bose ◽  
S.H. Zhang
Keyword(s):  
Spinal Cord ◽  
Early Stage ◽  
Cervical Spinal Cord ◽  
Wild Type Mouse ◽  
Reflex Response ◽  
Mouse Strains ◽  
Behavioral Tests ◽  
Wobbler Mouse ◽  
Stage 4 ◽  
Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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