The M603 idiotype is lost in the response to phosphocholine in terminal deoxynucleotidyl transferase-deficient mice

Mi, Qing Sheng; Rezanka, Louis J.; Lustig, Ana; Zhou, Li; Longo, Dan L.; Kenny, James J.

doi:10.1002/1521-4141(200204)32:4<1139::aid-immu1139>3.0.co;2-e

Cited by 4 publications

(1 citation statement)

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“…However, the primary source of adaptive antibody responses induced by pneumococcal polysaccharide, which are essential for long-term protection, has been attributed to the B-1b subset (Haas et al 2005). The robust PC and T-15 idiotypic responses to S. pneumoniae that we and others (Mi et al 2002) have shown in mice expressing Igs devoid of N-nucleotide addition were expected and likely due to the increased availability and abundance of germline-encoded canonical DFL16.1-containing CDR-H3s (Schelonka et al 2010; and manuscript in preparation). The converse appears to be true as well.…”

Section: Discussionsupporting

confidence: 53%

Absence of N addition facilitates B cell development, but impairs immune responses

et al. 2011

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The programmed, stepwise acquisition of immunocompetence that marks the development of the fetal immune response proceeds during a period when both T cell receptor and immunoglobulin (Ig) repertoires exhibit reduced junctional diversity due to physiologic terminal deoxynucleotidyl transferase (TdT) insufficiency. To test the effect of N addition on humoral responses, we transplanted bone marrow from TdT-deficient (TdT−/−) and wild-type (TdT+/+) BALB/c mice into recombination activation gene 1-deficient BALB/c hosts. Mice transplanted with TdT−/− cells exhibited diminished humoral responses to the T-independent antigens α-1-dextran and (2,4,6-trinitrophenyl) hapten conjugated to AminoEthylCarboxymethyl-FICOLL, to the T-dependent antigens NP19CGG and hen egg lysozyme, and to Enterobacter cloacae, a commensal bacteria that can become an opportunistic pathogen in immature and immunocompromised hosts. An exception to this pattern of reduction was the T-independent anti-phosphorylcholine response to Streptococcus pneumoniae, which is normally dominated by the N-deficient T15 idiotype. Most of the humoral immune responses in the recipients of TdT−/− bone marrow were impaired, yet population of the blood with B and T cells occurred more rapidly. To further test the effect of N-deficiency on B cell and T cell population growth, transplanted TdT-sufficient and -deficient BALB/c IgMa and congenic TdT-sufficient CB17 IgMb bone marrow were placed in competition. TdT−/− cells demonstrated an advantage in populating the bone marrow, the spleen, and the peritoneal cavity. TdT deficiency, which characterizes fetal lymphocytes, thus appears to facilitate filling both central and peripheral lymphoid compartments, but at the cost of altered responses to a broad set of antigens.Electronic supplementary materialThe online version of this article (doi:10.1007/s00251-011-0543-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 53%

Absence of N addition facilitates B cell development, but impairs immune responses

et al. 2011

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Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed

Kenny²

2013

Cell Mol Immunol

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Phosphocholine (PC) is the immunodominant epitope found on the surface of a number of microorganisms, including Streptococcus pneumoniae (SPn), and is thought to play a vital role in the pathogenesis of SPn. B cells expressing M167Hκ24L immunoglobulin receptors specific for PC have been shown to be autoreactive in that they undergo clonal deletion in both X-linked immune-deficient and Rag−/− mice. We have now shown that B cells expressing M603Hκ8L PC-specific receptors also delete in Rag−/− mice, whereas those expressing T15Hκ22L transgenes do not delete. However, T15Hκ22L B cells are lost in normal heterozygous transgenic mice because they cannot compete with normal B cells. These data indicate that M167Hκ24L and M603Hκ8L PC-specific B cells are recognizing an autoantigen expressed on membranes which causes them to downregulate their receptors and clonally delete, while T15Hκ22L B cells are tolerized by a soluble form of PC-antigen which results in their being trapped in the spleen. Thus, the types of tolerance seen in autoreactive PC-specific B cells are dependent on the idiotype of the receptors expressed.

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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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The M603 idiotype is lost in the response to phosphocholine in terminal deoxynucleotidyl transferase-deficient mice

Cited by 4 publications

References 39 publications

Absence of N addition facilitates B cell development, but impairs immune responses

Absence of N addition facilitates B cell development, but impairs immune responses

Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed

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

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