Biomedical subjects

S Desravines

Publications and source records attributed to S Desravines.

3 recordsLinked to original sources

PubMed1999

Junctional diversity in Xenopus immunoglobulin light chains.

Xenopus cDNA sequences encoding the homolog of mammalian kappa (kappa) light (L) chains were isolated from isogenic tadpole and adult individuals to investigate whether there existed stage-specific immunoglobulin L chain expression and somatic diversification. In the course of these studies rearrangements to a sixth J(L) gene segment and a pseudogene (J(L)psi) were found, and it is suggested that the order of these gene segments with respect to the L chain constant (C) region exon is: J(L)6-J(L)1-J(L)2-J(L)3-J(L)4-J(L)5-J(L)psi-C(L). The cDNA junctional diversity was analyzed; few N and P regions were found and almost all the CDR3 were 9 codons in length. There were restricted patterns of recombination site resolution, and this is attributed to some constraint in JL coding end processing.

Animals↗

PubMed1994

Measuring CDR3 length variability in individuals during ontogeny.

The portion of the antibody sequence that contributes most to the conformation of the antigen-combining site is the third complementarity-determining region (CDR3). The CDR3 in antibody heavy chains are somatically produced by the rearrangement of three different immunoglobulin (Ig) gene segments, VH, D and JH, and are therefore highly variable in sequence and length. We have devised a technique for rapid analysis of CDR3 length variability from a large number of cDNA samples. This technique allows comparative evaluation of IgH heterogeneity in individuals without recourse to DNA cloning and sequencing. We also present data on Ig sequences from different stages of development in the amphibian, Xenopus laevis. Most of the larval and post-metamorphic Ig samples contained CDR3 of 3-10 codons, two codons shorter than those of the adult CDR3, which were 5-12 codons. Antibodies may by immunized tadpoles have been shown to be much less diverse than those produced by adults to the same antigen. The shorter tadpole CDR3 perhaps generates a more limited spectrum of antigen-combining site structures and, in this way, makes for a more restricted antibody repertoire.

Animals↗

PubMed1993

IgH diversity in an individual with only one million B lymphocytes.

Immunoglobulin sequences from an individual Xenopus laevis froglet were analyzed for combinatorial and junctional diversity. In an animal with about 10(6) B lymphocytes, at least 26 out of the 56 VH1 genes available in a diploid genome were expressed, as were all JH segments. Junctional diversity was similar to that observed in Xenopus tadpole sequences, that is, little or no N diversification was found and the recombination site sometimes occurred in a region of V/D or D/J homology. The froglet IgH diversity is further restricted by the elimination of D-gene participation through direct V to J joining. Of the six complementary-determining regions (CDR) contributing to the structure of the antigen-combining site, CDR3 is the most variable in sequence and structure. Froglet IgH CDR3 are restricted to both aspects. Compared to IgH sequences isolated from a 5-month-old adult, froglet CDR3 were, on the average, two codons shorter; overall, 58% of the froglet Ig sequences isolated carried CDR3 of < or = 7 codons, compared to 30% of the adult sequences. In addition to being shorter, the tadpole/froglet CDR3 are less variable in sequence, as the absence of N regions also results in the V/D and D/J junctions being derived from germline elements. We therefore suggest that latent anti-adult specificities are not eliminated in situ, in the tadpole, but rather that such germline gene segments, singly or in their combinations thereof, that can potentially react to adult self-epitopes after metamorphosis have been counterselected during the course of evolution.

Animals↗