Functional Relationship Between T15 and J558 Idiotypes in BALB/c Mice

Vakil, Meenal; Kearney, John F.

doi:10.1155/1991/91729

Cited by 13 publications

(9 citation statements)

References 10 publications

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“…There is evidence supporting a role for B cell idiotypic interactions early in life that modulate the development of B cell clones responsive to DEX and to other T-independent antigens (56, 57). Neonatal injection of the anti-PC antibodies, such as the T15 antibody that is presumably more abundant in TdT−/− mice, leads to a reduction in J558 idiotype expression when these mice were immunized with DEX as adults (58). Therefore, the mechanism by which J558 Id expression requires TdTS may be indirect and involves the selection of J558-expressing clones as a result of B cell interactions with other B cells or other immune cells.…”

Section: Discussionmentioning

confidence: 99%

Terminal Deoxynucleotidyl Transferase Is Required for an Optimal Response to the Polysaccharide α-1,3 Dextran

Mahmoud

Kearney

2009

The Journal of Immunology

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An understanding of antibody responses to polysaccharides associated with pathogenic microorganisms is of importance for improving vaccine design, especially in neonates that respond poorly to these types of antigens. In this study, we have investigated the role of the lymphoid specific enzyme TdT in generating B cell clones responsive to α-1,3 Dextran (DEX). TdT is a DNA polymerase that plays a major role in generating diversity of lymphocyte antigen receptors during V(D)J recombination. In this study we show that the DEX-specific antibody response is lower and the dominant DEX-specific J558 idiotype (Id) is not detected in TdT−/− mice when compared to wild type BALB/c (WT) mice. Nucleotide sequencing of heavy chain CDR3s of DEX-specific plasmablasts, sorted post-immunization, showed that TdT−/− mice generate a lower frequency of the predominant adult molecularly-determined clone J558. Complementation of TdT expression in TdT−/− mice by early forced expression of the short splice variant of TdT restored WT proportions of J558 Id+ clones and also abrogated the development of the minor M104E Id+ clones. J558 Id V(D)J rearrangements are detected as early as 7 days after birth in IgM negative B cell precursors in the liver and spleen of WT and TdT transgenic mice but not in TdT−/− mice. These data show that TdT is essential for the generation of the predominant higher affinity DEX-responsive J558 clone.

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Section: Discussionmentioning

confidence: 99%

Terminal Deoxynucleotidyl Transferase Is Required for an Optimal Response to the Polysaccharide α-1,3 Dextran

Mahmoud

Kearney

2009

The Journal of Immunology

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“…These non-T15 antibodies also failed to confer prOtective immunity in recipient XID mice against virulent S. pneumoniae. We have further reported in a separate study that mice primed with R36A 2 days after birth also fail to respond to a structurally distinct but idiotypically linked antigen c1,3 dextran (Vakil and Kearney, 1991 Kearney, 1991). Therefore, the dominant expression T15 / B cells .…”

Section: Introductionmentioning

confidence: 84%

“…We have employed a modification of this assay (Hurwitz et al, 1982) We have previously reported the stimulatory effects of the anti-T15 antibody BD2 and the antianti-T15 antibody DB3, products of perinatal B-cell hybridomas (Bast et al, 1984; (Vakil and Kearney, 1991 Etlinger and Heusser, 1986), despite the ubiquitous nature of PC antigen,in the latter (Potter,, 1977 Chang et al (1984). These non-T15 antibodies also failed to confer prOtective immunity in recipient XID mice against virulent S. pneumoniae.…”

Section: Introductionmentioning

confidence: 99%

Antigen‐Independent Selection of T15 Idiotype During B‐Cell Ontogeny In Mice

Vakil

Briles

Kearney

1990

Journal of Immunology Research

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focus assays were detected in the spleens of neonatal mice as early as 4 days after birth. The earliest anti-PC B cells were T15-. T15 foci-forming B cells were first detected 6 days after birth and expanded rapidly to constitute greater than 80% of the total PC-specific foci by day 10. Injection of heat-killed S. pneumoniae (R36A) into neonatal mice resulted in priming of the antibody response to PC, with an idiotype profile reflecting that of precursors of foci-forming B cells at the time of antigen administration. Priming of 2-dayold mice with 2 X10 and 2 X10 R36A induced a five-and ten-fold increase in the antibody response to phosphorylcholine 6 to 8 weeks later. However, only 10 to 15% of the serum antibodies expressed the normally dominant T15 idiotype. Doses below 2 xl0 R36A showed no detectable priming activity. PC-specific hybridomas derived from mice injected with 2 X10 R36A 2 days after birth lacked the idiotypic and molecular characteristics typical of T15 antibodies. Antibodies to phosphorylcholine, raised by immunization of 6-week-old mice are normally protective against pneumococcal infection. However, serum antibodies from mice treated with R36A 2 days after birth and responding to phosphorylcholine following challenge with R36A at 6 weeks of age failed to protect against deliberate infection with virulent S. pneumoniae. These observations imply that the antigen phosphorylcholine does not play a role in the selective expansion and dominant expression of the T15 idiotype.

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“…Another possible problem with early vaccination of mice with polysaccharides may come from deleterious modulation of the murine antibody response (46,129,130). This effect is well demonstrated by the response to phosphocholine (PC).…”

Section: Immunogenic Considerations For Conjugate Vaccinesmentioning

confidence: 99%

“…In spite of these concerns, it must be pointed out that millions of infants have been immunized at 3 months of age with the H. influenzae group B polysaccharide-protein conjugate vaccines and there have been no reports of deleterious immunologic or developmental effects. For a pneumococcal vaccine, however, five or more different conjugates would be required, possibly increasing the risk of deleterious consequences, especially if they are dependent on idiotype network interactions that may interfere with B-cell differentiation (46,130).…”

Section: Immunogenic Considerations For Conjugate Vaccinesmentioning

confidence: 99%

Pneumococcal Diversity: Considerations for New Vaccine Strategies with Emphasis on Pneumococcal Surface Protein A (PspA)

Briles

Tart²,

Swiatlo³

et al. 1998

Clin Microbiol Rev

142

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SUMMARY Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.

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Functional Relationship Between T15 and J558 Idiotypes in BALB/c Mice

Cited by 13 publications

References 10 publications

Terminal Deoxynucleotidyl Transferase Is Required for an Optimal Response to the Polysaccharide α-1,3 Dextran

Terminal Deoxynucleotidyl Transferase Is Required for an Optimal Response to the Polysaccharide α-1,3 Dextran

Antigen‐Independent Selection of T15 Idiotype During B‐Cell Ontogeny In Mice

Pneumococcal Diversity: Considerations for New Vaccine Strategies with Emphasis on Pneumococcal Surface Protein A (PspA)

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