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Extensive CDR3H Length Heterogeneity Exists in Bovine Foetal VDJ Rearrangements
Author(s) -
Saini S. S.,
Kaushik A.
Publication year - 2002
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2002.01028.x
Subject(s) - germline , biology , somatic cell , genetics , somatic hypermutation , gene , gene rearrangement , gene conversion , pseudogene , gene duplication , microbiology and biotechnology , antibody , b cell , recombination , genome
Analysis of seven variable‐diversity‐joining (VDJ) gene rearrangements in B splenocytes from a 125‐day‐old bovine foetus revealed an extensive heavy‐chain complementarity‐determining region 3 (CDR3H) length variation (9–56 codons). Indeed, the global CDR3H size spectratyping of foetal VDJ rearrangements substantiated such an extensive heterogeneity and was comparable with that noted in peripheral B lymphocytes of adult cattle. These observations are in contrast to species such as humans with extensive germline combinatorial capability where shorter CDR3H length is noted early during B‐cell development. Exceptionally long CDR3H (as in adult cattle) was noted in two foetal VDJ rearrangements encoded by a single germline V H gene. Further, two V H genes (gl.110.20 and BF2B5) were preferentially expressed in the foetal VDJ rearrangements. The D H gene‐encoded CDR3H region of foetal VDJ rearrangements is remarkable for repetitive GGT (glycine) and TAT (tyrosine) codons that favour the recruitment of somatic hypermutations. It appears that closely related germline D H genes, preferentially used in the hydrophilic reading frame, encode varying CDR3H lengths early during B‐cell ontogeny in cattle. A comparison of germline and expressed V H genes, especially in the CDR1 and CDR2, confirms that somatic hypermutations contribute to immunoglobulin (Ig)M antibody diversification in cattle. The biased nucleotide base use and high occurrence of ‘hot‐spot’ triplet (AGPy; AG pyrimidine base) in the CDRs predisposes to somatic hypermutations. Overall, these observations suggest that extensive CDR3H length heterogeneity, including the generation of exceptionally long CDR3H (up to 56 amino acids), and somatic hypermutations contribute to IgM antibody diversification in cattle. The extensive CDR3H length heterogeneity early during the B‐cell development may compensate for constraints imposed on antibody diversification owing to the limited germline sequence diversity of genetic elements in cattle.