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Molecular immunogenetics of bovine antibody

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Title: Molecular immunogenetics of bovine antibody
Author: Saini, Surinder Singh
Department: Department of Pathobiology
Advisor: Kaushik, Azad
Abstract: A single predominantly expressed polymorphic bovine VH gene family (Bov VH1), comprising 13 to 15 genes, is identified in cattle. The Bov VH1 gene family is closest to the murine VH Q-52 and human VH4 gene families and related to evolutionarily less conserved mammalian group I VH genes. Approximately 9% of the VDJ rearrangements in B lymphocytes of adult cattle show exceptionally long CDR3H (56 to 61 codons) with multiple cysteine residues. Such an exceptionally long CDR3H in an antibody is the first ever to be documented in a species. The even numbered cysteine residues in the CDR3H appear to provide hitherto unknown configurational ability to the antigen combining site via probable intra-CDR3H disulfide bridging. The VDJ rearrangements with exceptionally long CDR3H are also noted in the splenic B cells of a 125-day-old fetus. Somatic hypermutations contribute significantly to the diversification of the IgM antibody repertoire in cattle. The bovine DH genes are preferentially used in the hydrophilic reading frame. The CDR3H region of fetal VDJ rearrangements shows repetitive GGT (glycine) and TAT (tyrosine) codons that seem to favour the recruitment of somatic hypermutations. The expressed bovine JH genes are most homologous to human JH4 and JH5 genes, suggesting the existence of, at least, two JH genes in cattle. The VDJ rearrangements resulting in exceptionally long CDR3H preferentially pair with either the V[lambda]1x gene or novel V[lambda]1 genes, designated as V[lambda]1d and V[lambda]1e subfamilies. Such preferential pairing may be related to unique conservation of alanine-serine-alanine residues in the V[lambda]1x, V[lambda]1d and V [lambda]1e gene encoded 3' region of the CDR3. The cDNA sequence of bovine C[mu] gene showed that sporadic nucleotide substitutions resulting in amino acid replacements provide a structural basis for bovine IgM allotypes. The retention of nucleotides at the CH1-CH2 junction from the intervening intron sequence, as a result of selection of an alternate splice donor site, provides an additional source of IgM variants. Bovine IgM has fewer proline residues at the CH1-CH2 junction which may result in low flexibility in this region as compared to other species. Southern blot analysis using a bovine C[mu] specific DNA probe revealed four allelic forms of the C[mu] gene in the bovine genome.
Date: 1999
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