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2. Older Human B Cells and Antibodies

Author

Dunn-Walters, Deborah K., O’Hare, Joselli Silva, Fulop, Tamas, Section editor, Fulop, Tamas, editor, Franceschi, Claudio, editor, Hirokawa, Katsuiku, editor, and Pawelec, Graham, editor

Published
2019
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4. Supplementary materials and methods and Supplementary figure legends revised from Tumor-Infiltrating B Lymphocyte Profiling Identifies IgG-Biased, Clonally Expanded Prognostic Phenotypes in Triple-Negative Breast Cancer

Author

Harris, Robert J., primary, Cheung, Anthony, primary, Ng, Joseph C.F., primary, Laddach, Roman, primary, Chenoweth, Alicia M., primary, Crescioli, Silvia, primary, Fittall, Matthew, primary, Dominguez-Rodriguez, Diana, primary, Roberts, James, primary, Levi, Dina, primary, Liu, Fangfang, primary, Alberts, Elena, primary, Quist, Jelmar, primary, Santaolalla, Aida, primary, Pinder, Sarah E., primary, Gillett, Cheryl, primary, Hammar, Niklas, primary, Irshad, Sheeba, primary, Van Hemelrijck, Mieke, primary, Dunn-Walters, Deborah K., primary, Fraternali, Franca, primary, Spicer, James F., primary, Lacy, Katie E., primary, Tsoka, Sophia, primary, Grigoriadis, Anita, primary, Tutt, Andrew N.J., primary, and Karagiannis, Sophia N., primary

Published
2023
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5. Supplementary tables and figures from Tumor-Infiltrating B Lymphocyte Profiling Identifies IgG-Biased, Clonally Expanded Prognostic Phenotypes in Triple-Negative Breast Cancer

Author

Harris, Robert J., primary, Cheung, Anthony, primary, Ng, Joseph C.F., primary, Laddach, Roman, primary, Chenoweth, Alicia M., primary, Crescioli, Silvia, primary, Fittall, Matthew, primary, Dominguez-Rodriguez, Diana, primary, Roberts, James, primary, Levi, Dina, primary, Liu, Fangfang, primary, Alberts, Elena, primary, Quist, Jelmar, primary, Santaolalla, Aida, primary, Pinder, Sarah E., primary, Gillett, Cheryl, primary, Hammar, Niklas, primary, Irshad, Sheeba, primary, Van Hemelrijck, Mieke, primary, Dunn-Walters, Deborah K., primary, Fraternali, Franca, primary, Spicer, James F., primary, Lacy, Katie E., primary, Tsoka, Sophia, primary, Grigoriadis, Anita, primary, Tutt, Andrew N.J., primary, and Karagiannis, Sophia N., primary

Published
2023
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11. Pandemic, Epidemic, Endemic: B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus

Author

Stewart, A, Sinclair, E, Ng, J, O'Hare, J, Page, A, Serangeli, I, Margreitter, C, Orsenigo, F, Longman, K, Frampas, C, Costa, C, Lewis, H, Kasar, N, Wu, B, Kipling, D, Openshaw, P, Chiu, C, Baillie, J, Scott, J, Semple, M, Bailey, M, Fraternali, F, Dunn-Walters, D, Stewart, Alexander, Sinclair, Emma, Ng, Joseph Chi-Fung, O'Hare, Joselli Silva, Page, Audrey, Serangeli, Ilaria, Margreitter, Christian, Orsenigo, Federica, Longman, Katherine, Frampas, Cecile, Costa, Catia, Lewis, Holly-May, Kasar, Nora, Wu, Bryan, Kipling, David, Openshaw, Peter Jm, Chiu, Christopher, Baillie, J Kenneth, Scott, Janet T, Semple, Malcolm G, Bailey, Melanie J, Fraternali, Franca, Dunn-Walters, Deborah K, Stewart, A, Sinclair, E, Ng, J, O'Hare, J, Page, A, Serangeli, I, Margreitter, C, Orsenigo, F, Longman, K, Frampas, C, Costa, C, Lewis, H, Kasar, N, Wu, B, Kipling, D, Openshaw, P, Chiu, C, Baillie, J, Scott, J, Semple, M, Bailey, M, Fraternali, F, Dunn-Walters, D, Stewart, Alexander, Sinclair, Emma, Ng, Joseph Chi-Fung, O'Hare, Joselli Silva, Page, Audrey, Serangeli, Ilaria, Margreitter, Christian, Orsenigo, Federica, Longman, Katherine, Frampas, Cecile, Costa, Catia, Lewis, Holly-May, Kasar, Nora, Wu, Bryan, Kipling, David, Openshaw, Peter Jm, Chiu, Christopher, Baillie, J Kenneth, Scott, Janet T, Semple, Malcolm G, Bailey, Melanie J, Fraternali, Franca, and Dunn-Walters, Deborah K

Abstract

Immunoglobulin gene heterogeneity reflects the diversity and focus of the humoral immune response towards different infections, enabling inference of B cell development processes. Detailed compositional and lineage analysis of long read IGH repertoire sequencing, combining examples of pandemic, epidemic and endemic viral infections with control and vaccination samples, demonstrates general responses including increased use of IGHV4-39 in both Zaire Ebolavirus (EBOV) and COVID-19 patient cohorts. We also show unique characteristics absent in Respiratory Syncytial Virus or yellow fever vaccine samples: EBOV survivors show unprecedented high levels of class switching events while COVID-19 repertoires from acute disease appear underdeveloped. Despite the high levels of clonal expansion in COVID-19 IgG1 repertoires there is a striking lack of evidence of germinal centre mutation and selection. Given the differences in COVID-19 morbidity and mortality with age, it is also pertinent that we find significant differences in repertoire characteristics between young and old patients. Our data supports the hypothesis that a primary viral challenge can result in a strong but immature humoral response where failures in selection of the repertoire risk off-target effects.

Published
2022

12. Pandemic, Epidemic, Endemic: B Cell Repertoire Analysis Reveals Unique Anti-Viral Responses to SARS-CoV-2, Ebola and Respiratory Syncytial Virus

Author

Stewart, Alexander, primary, Sinclair, Emma, additional, Ng, Joseph Chi-Fung, additional, O’Hare, Joselli Silva, additional, Page, Audrey, additional, Serangeli, Ilaria, additional, Margreitter, Christian, additional, Orsenigo, Federica, additional, Longman, Katherine, additional, Frampas, Cecile, additional, Costa, Catia, additional, Lewis, Holly-May, additional, Kasar, Nora, additional, Wu, Bryan, additional, Kipling, David, additional, Openshaw, Peter JM, additional, Chiu, Christopher, additional, Baillie, J Kenneth, additional, Scott, Janet T., additional, Semple, Malcolm G., additional, Bailey, Melanie J., additional, Fraternali, Franca, additional, and Dunn-Walters, Deborah K., additional

Published
2022
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20. Tumor-Infiltrating B Lymphocyte Profiling Identifies IgG-Biased, Clonally Expanded Prognostic Phenotypes in Triple-Negative Breast Cancer

Author

Harris, Robert J., primary, Cheung, Anthony, additional, Ng, Joseph C.F., additional, Laddach, Roman, additional, Chenoweth, Alicia M., additional, Crescioli, Silvia, additional, Fittall, Matthew, additional, Dominguez-Rodriguez, Diana, additional, Roberts, James, additional, Levi, Dina, additional, Liu, Fangfang, additional, Alberts, Elena, additional, Quist, Jelmar, additional, Santaolalla, Aida, additional, Pinder, Sarah E., additional, Gillett, Cheryl, additional, Hammar, Niklas, additional, Irshad, Sheeba, additional, Van Hemelrijck, Mieke, additional, Dunn-Walters, Deborah K., additional, Fraternali, Franca, additional, Spicer, James F., additional, Lacy, Katie E., additional, Tsoka, Sophia, additional, Grigoriadis, Anita, additional, Tutt, Andrew N.J., additional, and Karagiannis, Sophia N., additional

Published
2021
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28. Vitamin D status, body mass index, ethnicity and COVID-19: Initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723)

Author

Darling, Andrea L., primary, Ahmadi, Kourosh R., additional, Ward, Kate A, additional, Harvey, Nicholas C, additional, Alves, Alexessander Couto, additional, Dunn-Walters, Deborah K., additional, Lanham-New, Susan A., additional, Cooper, Cyrus, additional, and Blackbourn, David J., additional

Published
2020
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35. B-Cells and Antibodies in Old Humans

Author

Gibson, Kate L. and Dunn-Walters, Deborah K.

Subjects
Follicular Dendritic Cell, Influenza Vaccination, Germinal Centre, Respiratory Syncytial Virus, Affinity Maturation, Article
Abstract

It has been well established that the efficiency of the immune system declines with increasing age. Immunosenescence causes increased susceptibility to infectious diseases, and infection is, in fact, the third leading cause of mortality in people aged 65 and over [1]. As is clearly apparent from the other chapters of this book, there are many components of the immune system that can change with age, and are crucial to maintaining an effective immune system. The humoral immune system interacts with the other components, both as part of its own development and via its effector mechanisms. The most important function of B-cells is to produce antibodies, the indispensable soluble effectors of many functions. There are a number of different stages of development for B-cells and their antibodies (Fig. 1).

Published
2008

38. A Reassessment of IgM Memory Subsets in Humans

Author

Bagnara, Davide, primary, Squillario, Margherita, additional, Kipling, David, additional, Mora, Thierry, additional, Walczak, Aleksandra M., additional, Da Silva, Lucie, additional, Weller, Sandra, additional, Dunn-Walters, Deborah K., additional, Weill, Jean-Claude, additional, and Reynaud, Claude-Agnès, additional

Published
2015
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45. B-cell diversity decreases in old age and is correlated with poor health status

Author

Gibson, Kate L, Duggan, Orla, Vaughan, Robert, Kondeatis, Elli, Nilsson, Bengt-Olof, Wikby, Anders, Kipling, David, Dunn-Walters , Deborah K, Gibson, Kate L, Duggan, Orla, Vaughan, Robert, Kondeatis, Elli, Nilsson, Bengt-Olof, Wikby, Anders, Kipling, David, and Dunn-Walters , Deborah K

Abstract

Older people suffer from a decline in immune system, which affects their ability to respond to infections and to raise efficient responses to vaccines. Effective and specific antibodies in responses from older individuals are decreased in favour of non-specific antibody production. We investigated the B-cell repertoire in DNA samples from peripheral blood of individuals aged 86-94 years, and a control group aged 19-54 years, using spectratype analysis of the IGHV complementarity determining region (CDR)3. We found that a proportion of older individuals had a dramatic collapse in their B-cell repertoire diversity. Sequencing of polymerase chain reaction products from a selection of samples indicated that this loss of diversity was characterized by clonal expansions of B cells in vivo. Statistical analysis of the spectratypes enabled objective comparisons and showed that loss of diversity correlated very strongly with the general health status of the individuals; a distorted spectratype can be used to predict frailty. Correlations with survival and vitamin B12 status were also seen. We conclude that B-cell diversity can decrease dramatically with age and may have important implications for the immune health of older people. B-cell immune frailty is also a marker of general frailty.

Published
2009
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48. Functional Versatility of AGY serine Codons in immunoglobulin Variable region Genes.

Author

Detanico, Thiago, Phillips, Matthew, Wysocki, Lawrence J., Zemlin, Michael, Dunn-Walters, Deborah K., and Ippolito, Gregory C.

Subjects
IMMUNOGLOBULINS, SOMATIC mutation, GENETIC code
Abstract

In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ags) often arise by somatic hypermutation (SHM) that converts AGT and AGC (AGY) Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs) of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes. Because AGC is a preferred target for SHM by activation-induced cytidine deaminase, we asked whether the AGY abundance was solely due to a selection pressure to conserve high mutability in CDRs regardless of codon context but found that this was not the case. Instead, AGY triplets were selectively enriched in the Ser codon reading frame. Motivated by reports implicating a functional role for poly/autoreactive specificities in antiviral antibodies, we also analyzed mutations at AGY in antibodies directed against a number of different viruses and found that mutations producing Arg codons in antiviral antibodies were indeed frequent. Unexpectedly, however, we also found that AGY codons mutated often to encode nearly all of the amino acids that are reported to provide the most frequent contacts with Ag. In many cases, mutations producing codons for these alternative amino acids in antiviral antibodies were more frequent than those producing Arg codons. Mutations producing each of these key amino acids required only single-base changes in AGY. AGY is the only codon group in which two-thirds of random mutations generate codons for these key residues. Finally, by directly analyzing X-ray structures of immune complexes from the RCSB protein database, we found that Ag-contact residues generated via SHM occurred more often at AGY than at any other codon group. Thus, preservation of AGY codons in antibody genes appears to have been driven by their exceptional functional versatility, despite potential autoreactive consequences. [ABSTRACT FROM AUTHOR]

Published
2016
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49. Age-related aspects of human IgM+ B cell heterogeneity.

Author

Martin, Victoria, Wu, Yu‐Chang, Kipling, David, and Dunn‐Walters, Deborah K.

Subjects
B cells, CD27 antigen, POLYSACCHARIDES, STIMULUS & response (Biology), IMMUNOGLOBULIN D, PATHOGENIC bacteria, PHENOTYPES
Abstract

The CD27+IgD+ B cell population, known as IgM memory, reduces with age. It is thought that this population is responsible for pneumococcal polysaccharide T-independent responses, and that the age-related reduction might be partially responsible for the increased susceptibility of older people to bacterial pathogens. There are other IgM+ B cell populations that do not express IgD. We compared the different IgM populations using high-throughput sequencing of the immunoglobulin (Ig) gene repertoire and multidimensional cell phenotyping and found that the different populations of IgM cells, defined by CD27 and IgD expression, have repertoire differences. Some of these differences are likely indicative of different selection pressures in an immune response, although the older individuals were found to have a changed repertoire in naive B cells, which may contribute to some of the changes seen in memory cells. In addition, even within the CD27+IgD+ IgM memory population there are multiple cell types. We show that the level of IgM expression varies substantially and hypothesize that this distinguishes between T-dependent and T-independent types of IgM memory cells. Significant age-related changes in the relative proportions of these populations may exacerbate the reduction in T-independent responders in old age. [ABSTRACT FROM AUTHOR]

Published
2015
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