Identification of Antigen-Specific B Cell Receptor Sequences Using Public Repertoire Analysis

Trück, Johannes; Ramasamy, Maheshi; Galson, Jacob D.; Rance, Richard; Parkhill, Julian; Lunter, Gerton; Pollard, Andrew J.; Kelly, Dominic F.

doi:10.4049/jimmunol.1401405

Cited by 113 publications

(116 citation statements)

References 60 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…For example, IGHV1-69 is repeatedly implicated in next-generation studies of anti-viral antibody repertoires (for example, influenza and HIV-1), and the ‘inherently autoreactive' IGHV4-34 element is associated with a range of autoimmune disorders (for example, cold agglutinin disease and systemic lupus erythematosus). Indeed, convergent, or ‘public', responses using these IGHV gene segments coupled within homologous CDR-H3 clonotypes continue to be discovered343536.…”

Section: Discussionmentioning

confidence: 99%

Temporal stability and molecular persistence of the bone marrow plasma cell antibody repertoire

Cheung

Georgiou

et al. 2016

Nat Commun

View full text Add to dashboard Cite

Plasma cells in human bone marrow (BM) are thought to be responsible for sustaining lifelong immunity, but its underlying basis is controversial. Here we use high-throughput sequence analysis of the same individual across 6.5 years to show that the BM plasma cell immunoglobulin heavy chain repertoire is remarkably stable over time. We find a nearly static bias in individual and combinatorial gene usage across time. Analysis of a second donor corroborates these observations. We also report the persistence of numerous BM plasma cell clonotypes (∼2%) identifiable at all points assayed across 6.5 years, supporting a model of serological memory based upon intrinsic longevity of human plasma cells. Donors were adolescents who completely recovered from neuroblastoma prior to the start of this study. Our work will facilitate differentiation between healthy and diseased antibody repertoires, by serving as a point of comparison with future deep-sequencing studies involving immune intervention.

show abstract

Section: Discussionmentioning

confidence: 99%

Temporal stability and molecular persistence of the bone marrow plasma cell antibody repertoire

Cheung

Georgiou

et al. 2016

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Productive sequences were analyzed according to the composition and characteristics of inverse Simpson’s index (1/DS), overlapping CDR3, and high frequency CDR3 [14–17]. The diversity of clonotypes was calculated using inverse Simpson's index, using the formula D s = 1 − Σ[ n i ( n i − 1)]/[ N ( N − 1)], where n i is the clone size of the i th clonotype and N is the total number of sequence reads [16,17].…”

Section: Methodsmentioning

confidence: 99%

Characteristics Peripheral Blood IgG and IgM Heavy Chain Complementarity Determining Region 3 Repertoire before and after Immunization with Recombinant HBV Vaccine

Wang

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

Immunization with recombinant HBV vaccine induces specific immune responses in human causing B lymphocytes to produce protective HBsAb, and to form memory B lymphocytes, thereby facilitating HBV immunity in the body. However, B lymphocytes heterogeneity and characteristics are not fully elucidated. In this study, we conducted high-throughput sequencing of BCR heavy chain CDR3 repertoires in 3 healthy volunteers before and after the third immunization with recombinant HBV vaccine. We used Roche 454 Genome Sequencer FLX system to perform a comparative analysis of IgM and IgG H chain CDR3 repertoires. First, we found that the diversity of IgG H chain CDR3 repertoires was 1/6 of IgM on average. Moreover, after the third immunization with HBV vaccine, the diversity of IgG H chain CDR3 repertoires was 1/26 of IgM on average. Second, we detected relatively high levels of HBsAbs in all the healthy volunteers after immunization with HBV vaccine. The volunteers shared a small number of CDR3 sequences before and after immunization, and among each other. However, we did not find completely identical BCR H chain CDR3 amino acid sequences in these volunteers. Lastly, after immunization with recombinant HBV vaccine, the volunteers showed high frequency of IgG H chain CDR3 amino acid sequences mostly resulting from rearrangements of IGHV, IGHD and IGHJ, suggesting that the mechanism of high frequency CDR3 generation might be associated with the maturation of IgG affinity (somatic hypermutation) during the recombinant HBV vaccine-induced B lymphocyte responses. This study identified the characteristics and changes of BCR CDR3 repertoires before and after immunization with HBV vaccine, and evaluated the performance of the sequencing technology for this application. Our findings provide a basis for further research in B lymphocyte generated HBsAb heterogeneity and monitoring the maintenance of memory B lymphocytes.

show abstract

“…Thus, even though similar infection histories may lead to similar patterns of immunodominance between individuals, differences remain. By contrast, seemingly diverse responses may eventually converge via evolution, as seen in dengue [42], HIV [43] and influenza [41,45,96,125]. Zarnitsyna et al [126] in this issue investigate competition between B cells in a setting that models antigenic drift and shift in influenza, including multiple antigenic sites.…”

Section: Growth and Competition Among The Clonesmentioning

confidence: 99%

“…For instance, in a small fraction of people infected with the human immunodeficiency virus (HIV) [21][22][23] [39,40], and genotypic or phenotypic convergence [41][42][43][44][45], but the relative importance of each is not yet clear.…”

Section: Introductionmentioning

confidence: 99%

The evolution within us

Cobey

Wilson

Matsen

2015

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

One contribution of 13 to a theme issue 'The dynamics of antibody repertoires'. The B-cell immune response is a remarkable evolutionary system found in jawed vertebrates. B-cell receptors, the membrane-bound form of antibodies, are capable of evolving high affinity to almost any foreign protein. High germline diversity and rapid evolution upon encounter with antigen explain the general adaptability of B-cell populations, but the dynamics of repertoires are less well understood. These dynamics are scientifically and clinically important. After highlighting the remarkable characteristics of naive and experienced B-cell repertoires, especially biased usage of genes encoding the B-cell receptors, we contrast methods of sequence analysis and their attempts to explain patterns of B-cell evolution. These phylogenetic approaches are currently unlinked to explicit models of B-cell competition, which analyse repertoire evolution at the level of phenotype, the affinities and specificities to particular antigenic sites. The models, in turn, suggest how chance, infection history and other factors contribute to different patterns of immunodominance and protection between people. Challenges in rational vaccine design, specifically vaccines to induce broadly neutralizing antibodies to HIV, underscore critical gaps in our understanding of B cells' evolutionary and ecological dynamics.

show abstract

Identification of Antigen-Specific B Cell Receptor Sequences Using Public Repertoire Analysis

Cited by 113 publications

References 60 publications

Temporal stability and molecular persistence of the bone marrow plasma cell antibody repertoire

Temporal stability and molecular persistence of the bone marrow plasma cell antibody repertoire

Characteristics Peripheral Blood IgG and IgM Heavy Chain Complementarity Determining Region 3 Repertoire before and after Immunization with Recombinant HBV Vaccine

The evolution within us

Contact Info

Product

Resources

About