Bos taurus genome sequence reveals the assortment of immunoglobulin and surrogate light chain genes in domestic cattle

Ekman, Anna; Niku, Mikael; Liljavirta, Jenni; Iivanainen, Antti

doi:10.1186/1471-2172-10-22

Cited by 28 publications

(53 citation statements)

References 37 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data are highly suggestive of AIDdependent SHM in the fetal bovine IPP and spleen before exposure to exogenous antigens and imply a specific molecular mechanism to diversify the limited germline Ig repertoire. 27,34 Statistical analysis indicated strong selection of the mutated IGHV sequences in the fetal IPP and spleen ( Table 2). Negative Table 1.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens

et al. 2013

View full text Add to dashboard Cite

Due to a limited range of immunoglobulin (Ig) genes, cattle and several other domestic animals rely on postrecombinatorial amplification of the primary repertoire. We report that activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen but not in fetal bone marrow. The numbers of IGHV (immunoglobulin heavy chain variable) mutations correlate with AID expression. The mutational profile in the fetuses is similar to postnatal and immunized calves, with targeting of complementarity-determining region (CDR) over framework region (FR), preference of replacement over silent mutations in CDRs but not in FRs, and targeting of the AID hotspot motif RGYW/WRCY. Statistical analysis indicates negative selection on FRs and positive selection on CDRs. Our results suggest that AID-mediated somatic hypermutation and selection take place in bovine fetuses, implying a role for AID in the diversification of the primary antibody repertoire in the absence of exogenous antigens.

show abstract

Section: Discussionmentioning

confidence: 99%

“…27,34 Antibody-diversifying mechanisms in addition to recombination are therefore likely to exist. Previous studies have suggested that these may include SHM, 6,36 GC, 7 and junctional diversity.…”

Section: Discussionmentioning

confidence: 99%

Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens

et al. 2013

View full text Add to dashboard Cite

show abstract

“…All non-ribosomal reads were mapped to a library containing the Bos taurus germline V, D and J genes [19, 20] (courtesy of authors Antti Livanainen and Ulrike S. Diesterbeck), and mature antibody sequences were retrieved from the DIGIT database [21] using TopHat2 software with relaxed parameters allowing for up to 30 mismatches, 50 gaps, and both should sum up to an overall edit distance of no more than 60. This was done to take into account somatic mutations and possible missing germ lines in the currently sequenced bovine antibody gene repertoire.…”

Section: Methodsmentioning

confidence: 99%

A novel approach to probe host-pathogen interactions of bovine digital dermatitis, a model of a complex polymicrobial infection

et al. 2016

View full text Add to dashboard Cite

BackgroundPolymicrobial infections represent a great challenge for the clarification of disease etiology and the development of comprehensive diagnostic or therapeutic tools, particularly for fastidious and difficult-to-cultivate bacteria. Using bovine digital dermatitis (DD) as a disease model, we introduce a novel strategy to study the pathogenesis of complex infections.ResultsThe strategy combines meta-transcriptomics with high-density peptide-microarray technology to screen for in vivo-expressed microbial genes and the host antibody response at the site of infection. Bacterial expression patterns supported the assumption that treponemes were the major DD pathogens but also indicated the active involvement of other phyla (primarily Bacteroidetes). Bacterial genes involved in chemotaxis, flagellar synthesis and protection against oxidative and acidic stress were among the major factors defining the disease.ConclusionsThe extraordinary diversity observed in bacterial expression, antigens and host antibody responses between individual cows pointed toward microbial variability as a hallmark of DD. Persistence of infection and DD reinfection in the same individual is common; thus, high microbial diversity may undermine the host’s capacity to mount an efficient immune response and maintain immunological memory towards DD. The common antigenic markers identified here using a high-density peptide microarray address this issue and may be useful for future preventive measures against DD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3341-7) contains supplementary material, which is available to authorized users.

show abstract

“…The Ig heavy reverse external primer was designed to amplify only Igγ1 and Igγ2 genes since Igγ3 is not expressed at the protein level 55 . In addition, because the bovine immune system expresses Ig lambda chain preferentially, 56 in this study, the Ig light reverse external primer targets all lambda genes (Ig λ 1–4) but not kappa chain genes. Out of 95 cells, 42 cells showed an Ig heavy V gene band, but the Ig lambda V gene for only 39 cells could be amplified (positive for both heavy and light V gene) and selected for sub-cloning and expression cloning.…”

Section: Resultsmentioning

confidence: 99%

Trimeric gp120-specific bovine monoclonal antibodies require cysteine and aromatic residues in CDRH3 for high affinity binding to HIV Env

Heydarchi

Bebbington

Cuthbertson

et al. 2016

mAbs

View full text Add to dashboard Cite

We isolated HIV-1 Envelope (Env)-specific memory B cells from a cow that had developed high titer polyclonal immunoglobulin G (IgG) with broad neutralizing activity after a long duration vaccination with HIV-1AD8 Env gp140 trimers. We cloned the bovine IgG matched heavy (H) and light (L) chain variable (V) genes from these memory B cells and constructed IgG monoclonal antibodies (mAbs) with either a human constant (C)-region/bovine V-region chimeric or fully bovine C and V regions. Among 42 selected Ig+ memory B cells, two mAbs (6A and 8C) showed high affinity binding to gp140 Env. Characterization of both the fully bovine and human chimeric isoforms of these two mAbs revealed them as highly type-specific and capable of binding only to soluble AD8 uncleaved gp140 trimers and covalently stabilized AD8 SOSIP gp140 cleaved trimers, but not monomeric gp120. Genomic sequence analysis of the V genes showed the third heavy complementarity-determining region (CDRH3) of 6A mAb was 21 amino acids in length while 8C CDRH3 was 14 amino acids long. The entire V heavy (VH) region was 27% and 25% diverged for 6A and 8C, respectively, from the best matched germline V genes available, and the CDRH3 regions of 6A and 8C were 47.62% and 78.57% somatically mutated, respectively, suggesting a high level of somatic hypermutation compared with CDRH3 of other species. Alanine mutagenesis of the VH genes of 6A and 8C, showed that CDRH3 cysteine and tryptophan amino acids were crucial for antigen binding. Therefore, these bovine vaccine-induced anti-HIV antibodies shared some of the notable structural features of elite human broadly neutralizing antibodies, such as CDRH3 size and somatic mutation during affinity-maturation. However, while the 6A and 8C mAbs inhibited soluble CD4 binding to gp140 Env, they did not recapitulate the neutralizing activity of the polyclonal antibodies against HIV infection.

show abstract

Bos taurus genome sequence reveals the assortment of immunoglobulin and surrogate light chain genes in domestic cattle

Abstract: Background: The assortment of cattle immunoglobulin and surrogate light chain genes has been extracted from the version 3.1 of Bos taurus genome sequence as a part of an international effort to sequence and annotate the bovine genome.

Cited by 28 publications

References 37 publications

Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens

Activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen and is associated with expansion of the primary antibody repertoire in the absence of exogenous antigens

A novel approach to probe host-pathogen interactions of bovine digital dermatitis, a model of a complex polymicrobial infection

Trimeric gp120-specific bovine monoclonal antibodies require cysteine and aromatic residues in CDRH3 for high affinity binding to HIV Env

Contact Info

Product

Resources

About