Uniformity in the clonal repertoire for the immune response to phosphorylcholine in mice

Claflin, J L

doi:10.1002/eji.1830061002

Cited by 66 publications

(43 citation statements)

References 40 publications

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“…This serum has been shown to lack protective antibodies to phosphocholine (7). Non-CBA/N mouse serum contains natural antibodies reactive with teichoic acids (12,13). These antibodies, especially those of the IgG isotypes can be protective (4,5).…”

Section: Analysis Of Complement Deposition On Pspamentioning

confidence: 99%

Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface

Ren¹,

et al. 2004

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Streptococcus pneumoniae infection is a frequent cause of pneumonia, otitis media, meningitis, and septicemia. Pneumococcal surface protein A (PspA) is an important virulence factor on the pathogen surface, and it is known to interfere with complement activation. In this study, flow cytometry was used to study the effects of PspA and antibodies to PspA on the deposition of complement C3 on the surface of a capsular type 3 strain, WU2, and its PspA ؊ mutant, JY1119. Using naive mouse serum as a complement source, measurable deposition of C3 was observed within 4 min on PspA ؊ pneumococci, and the amount of surface-bound C3 accumulated rapidly as the amount of serum was increased. In contrast, very little C3 was deposited on the PspA ؉ strain. In nonimmune mouse serum, the classical pathway was the dominant activation pathway triggered by PspA ؊ pneumococci. Accordingly, EGTA blocked almost all of the complement activation. Moreover, a significant amount of C3 was still deposited on the PspA ؊ strain when serum from factor B-deficient mice was used. This deposition was not observed on the PspA ؉ pneumococci, indicating that PspA may inhibit complement deposition via the classical pathway. Furthermore, under the conditions we tested, PspA also inhibited C3 deposition when the classical pathway was initiated by antibodies to capsular polysaccharide. Antibodies to PspA could overcome the anticomplementary effect of PspA, allowing for increased complement activation and C3 deposition onto PspA ؉ bacteria.

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Section: Analysis Of Complement Deposition On Pspamentioning

confidence: 99%

Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface

Ren¹,

et al. 2004

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“…In the response to phosphorylcholine (PCho) of the BALB/c mouse which is characterized by dominance of the HOPC-8 (H8) idiotype (9)(10)(11)(12)(13), it has been shown that liver, spleen, and bone marrow of the neonate do not contain PCho-specific precursor cells. At age 1 week, the H8 clone appears in the spleen and bone marrow (14).…”

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confidence: 99%

Clonal dominance: loss and restoration in adoptive transfer.

Kaplan

Quintáns

Köhler

1978

Proc. Natl. Acad. Sci. U.S.A.

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“…The immune response to phosphocholine involves at least three different types of K light chains represented by the myelomas TEPC15, M603, and M511/M167 (21,22 Somatic diversification mechanisms had previously been proposed in the A light chain immunoglobulin system from a comparison of DNA molecular hybridization data with the amino acid sequences of several myeloma proteins (23,24). In short, several proteins appear to be derived from only a few (or one) VA genes (25,26) What somatic mechanisms could explain the generation of the M511 or M167 sequence and these other somatic variants from the single-copy prototype VK24 germ-line gene?…”

Section: Discussionmentioning

confidence: 99%

Somatic diversification is required to generate the V kappa genes of MOPC 511 and MOPC 167 myeloma proteins.

Gershenfeld¹,

Tsukamoto²,

Weissman³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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The immune response to phosphocholine in BALB/c mice involves one group of heavy chain variable region (VH) genes and at least three groups of light chain variable region (VK) genes, represented by the gene products of the myelomas TEPC 15, MOPC 603, and MOPC 167/MOPC 511. The amino acid sequences of BALB/c myeloma c chains MOPC 167 and MOPC 511 are known, and they differ by six amino acids. We have isolated several closely related V region genes of immunoglobulin light chains from a mouse sperm DNA phage library, selecting clones that cross-hybridize with a cDNA plasmid probe encoding the light chain of MOPC 167. We identified six strongly hybridizing clones, representing three separate cloning events. We determined the sequence of the coding and immediate flanking regions of three clones, representing the three separate cloning events, and they proved to be identical. This germ-line sequence encoded the amino acid sequence ofneither MOPC 167 nor MOPC 511, but required four base pair changes to generate the VM167 cDNA sequence and five base pair changes to generate the VcM5ll gene. By Southern hybridization experiments, we demonstrated that neither MOPC 511 nor MOPC 167 germ-line genes exist. We conclude that the VM167 and VKM511 genes are created somatically.An immunoglobulin polypeptide contains two distinct regions, the variable (V) and the constant (C) regions. The variability of amino acid sequences within the V region determines the antigen-binding specificity of the antibody. To explain the origin of antibody diversity, the germline hypothesis proposed that diversity arises from the multiplicity of the V region genes encoded in the germ line, whereas the somatic mutation hypothesis proposed that diversity arises from a few inherited germline genes, which during the life of an individual (ontogeny) undergo somatic variations to create an expanded repertoire of V genes (1-7).From molecular hybridization (and Southern blotting) data gathered by using subgroup-specific VK or VH probes (H, heavy chain), the number of cross-hybridizing germ-line V genes is estimated to range between 4 and 20 genes per subgroup, with 100 VK subgroups (8). However, the question of how much expressed antibody diversity is encoded in the germ-line V genes and how much, if any, is attributable to somatic mechanisms remains unanswered.Previously, we characterized the organization of the VKM167 gene family in germ-line DNA by Southern blotting, and we demonstrated that no major changes in the size of the VKM167-related genes occur during embryogenesis, ruling out embryonic episomal insertion of genetic elements (9). In this paper, we describe the isolation of several closely related VK gene clones from a A phage library of mouse sperm DNA by probing with a MOPC 167 (M167) light chain cDNA (pl67kRI). Because both VKM167 and VKM511 genes belong to the VK24 light chain subgroup, we shall refer to genomic germ-line clones hybridizing to pl67kRI as VK24 genes. We have determined the entire nucleotide sequence of the coding and im...

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Uniformity in the clonal repertoire for the immune response to phosphorylcholine in mice

Cited by 66 publications

References 40 publications

Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface

Effects of PspA and Antibodies to PspA on Activation and Deposition of Complement on the Pneumococcal Surface

Clonal dominance: loss and restoration in adoptive transfer.

Somatic diversification is required to generate the V kappa genes of MOPC 511 and MOPC 167 myeloma proteins.

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