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Martin VG, Wu YB, Townsend CL, et al. Transitional B Cells in Early Human B Cell Development - Time to Revisit the Paradigm?. Front Immunol. 2016;7:546doi: 10.3389/fimmu.2016.00546.
Martin, V. G., Wu, Y. B., Townsend, C. L., Lu, G. H., O'Hare, J. S., Mozeika, A., Coolen, A. C., Kipling, D., Fraternali, F., & Dunn-Walters, D. K. (2016). Transitional B Cells in Early Human B Cell Development - Time to Revisit the Paradigm?. Frontiers in immunology, 7546. https://doi.org/10.3389/fimmu.2016.00546
Martin, Victoria G, et al. "Transitional B Cells in Early Human B Cell Development - Time to Revisit the Paradigm?." Frontiers in immunology vol. 7 (2016): 546. doi: https://doi.org/10.3389/fimmu.2016.00546
Martin VG, Wu YB, Townsend CL, Lu GH, O'Hare JS, Mozeika A, Coolen AC, Kipling D, Fraternali F, Dunn-Walters DK. Transitional B Cells in Early Human B Cell Development - Time to Revisit the Paradigm?. Front Immunol. 2016 Dec 02;7:546. doi: 10.3389/fimmu.2016.00546. eCollection 2016. PMID: 27994589; PMCID: PMC5133252.
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Front Immunol. 2016 Dec 02;7:546. doi: 10.3389/fimmu.2016.00546. eCollection 2016.

Transitional B Cells in Early Human B Cell Development - Time to Revisit the Paradigm?.

Frontiers in immunology

Victoria G Martin, Yu-Chang Bryan Wu, Catherine L Townsend, Grace H C Lu, Joselli Silva O'Hare, Alexander Mozeika, Anthonius C C Coolen, David Kipling, Franca Fraternali, Deborah K Dunn-Walters

Affiliations

  1. Division of Infection, Immunity and Inflammatory Disease, Faculty of Life Sciences & Medicine, King's College London , London , UK.
  2. Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences & Medicine, King's College London , London , UK.
  3. Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey , Guildford, Surrey , UK.
  4. Faculty of Life Sciences & Medicine, Institute for Mathematical and Molecular Biomedicine, King's College London , London , UK.
  5. Institute of Cancer and Genetics, School of Medicine, Cardiff University , Cardiff , UK.
  6. Randall Division of Cell and Molecular Biophysics, Faculty of Life Sciences & Medicine, King's College London, London, UK; Faculty of Life Sciences & Medicine, Institute for Mathematical and Molecular Biomedicine, King's College London, London, UK.
  7. Division of Infection, Immunity and Inflammatory Disease, Faculty of Life Sciences & Medicine, King's College London, London, UK; Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, Surrey, UK.

PMID: 27994589 PMCID: PMC5133252 DOI: 10.3389/fimmu.2016.00546

Abstract

The B cell repertoire is generated in the adult bone marrow by an ordered series of gene rearrangement processes that result in massive diversity of immunoglobulin (Ig) genes and consequently an equally large number of potential specificities for antigen. As the process is essentially random, the cells exhibiting excess reactivity with self-antigens are generated and need to be removed from the repertoire before the cells are fully mature. Some of the cells are deleted, and some will undergo receptor editing to see if changing the light chain can rescue an autoreactive antibody. As a consequence, the binding properties of the B cell receptor are changed as development progresses through pre-B ≫ immature ≫ transitional ≫ naïve phenotypes. Using long-read, high-throughput, sequencing we have produced a unique set of sequences from these four cell types in human bone marrow and matched peripheral blood, and our results describe the effects of tolerance selection on the B cell repertoire at the Ig gene level. Most strong effects of selection are seen within the heavy chain repertoire and can be seen both in gene usage and in CDRH3 characteristics. Age-related changes are small, and only the size of the CDRH3 shows constant and significant change in these data. The paucity of significant changes in either kappa or lambda light chain repertoires implies that either the heavy chain has more influence over autoreactivity than light chain and/or that switching between kappa and lambda light chains, as opposed to switching within the light chain loci, may effect a more successful autoreactive rescue by receptor editing. Our results show that the transitional cell population contains cells other than those that are part of the pre-B ≫ immature ≫ transitional ≫ naïve development pathway, since the population often shows a repertoire that is outside the trajectory of gene loss/gain between pre-B and naïve stages.

Keywords: B cell development; bone marrow; human; regulatory B cells; transitional

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