Characterization of the Highly Prevalent Regulatory CD24CD38 B-Cell Population in Human Cord Blood

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2017 Mar 23

PMID 28326080

Citations 13

Authors

Ana Esteve-Sole

Irene Teixido

Angela Deya-Martinez

Jordi Yague

Ana M Plaza-Martin

Manel Juan

Laia Alsina

Affiliations

Soon will be listed here.

Abstract

The newborn's immune system must transition from a sterile haploidentical uterus to the world full of antigens. Regulatory B-cells (Breg; broadly defined as CD19CD24CD38) are tolerance promoters in the adult immune system. They can inhibit IFN-γ and IL-17 production by T-cells and are essential in different conditions, including pregnancy. Breg have still not been well characterized in umbilical cord blood, where we hypothesize that they are pivotal in the achievement of tolerance. We studied CD19CD24CD38 Breg in healthy umbilical cord blood (hUCB) compared to healthy peripheral adult blood (hAPB). Total numbers of Breg were increased in hUCB compared to hAPB (34.39 vs. 9.49%; = 0.0002), especially in the marginal zone-like B-cell subset, in which the most marked difference could be observed between hUCB and hAPB (60.80 vs. 4.94%; = 0.1). CD24CD38 subset in hUCB produced IL-10 and inhibited T-cell IFN-γ [1.63 vs. 0.95 stimulation ratio (SR); = 0.004] and IL-4 (1.63 vs. 1.44 SR; = 0.39) production. Phenotypically, hUCB Breg cells presented IgMIgDCD5CD10CD27 markers, similar to those described in hAPB Breg cells, but they showed increased IgM concentration and decreased expression of CD22 and CD73 markers. Our work characterized the frequency, phenotype, and function of Breg in hUCB, which may contribute to understanding of immune tolerance during pregnancy, paving the way to a new approach to immune-related diseases in the fetus and the newborn.

Citing Articles

B cells: roles in physiology and pathology of pregnancy.

Liu J, Zeng Q, Duan Y, Yeung W, Li R, Ng E Front Immunol. 2024; 15:1456171.

PMID: 39434884 PMC: 11491347. DOI: 10.3389/fimmu.2024.1456171.

Changes in Treg and Breg cells in a healthy pediatric population.

Luo Y, Acevedo D, Vlagea A, Codina A, Garcia-Garcia A, Deya-Martinez A Front Immunol. 2023; 14:1283981.

PMID: 38077340 PMC: 10704817. DOI: 10.3389/fimmu.2023.1283981.

B cell receptor-induced IL-10 production from neonatal mouse CD19CD43 cells depends on STAT5-mediated IL-6 secretion.

Sakai J, Yang J, Chou C, Wu W, Akkoyunlu M Elife. 2023; 12.

PMID: 36735294 PMC: 9934864. DOI: 10.7554/eLife.83561.

The adaptive immune system in early life: The shift makes it count.

Pieren D, Boer M, Wit J Front Immunol. 2022; 13:1031924.

PMID: 36466865 PMC: 9712958. DOI: 10.3389/fimmu.2022.1031924.

Peripheral CD5+ CD10+ B-cell proliferation with atypical morphology attributable to human herpesvirus 6 infection following umbilical cord blood transplantation.

Canali A, Rieu J, Bain B Am J Hematol. 2022; 97(11):1489-1490.

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References

Chen Q, Zhu X, Chen R, Liu J, Liu P, Hu A . Early Pregnancy Factor Enhances the Generation and Function of CD4CD25 Regulatory T Cells. Tohoku J Exp Med. 2016; 240(3):215-220. DOI: 10.1620/tjem.240.215. View

Schatorje E, Gemen E, Driessen G, Leuvenink J, van Hout R, de Vries E . Paediatric reference values for the peripheral T cell compartment. Scand J Immunol. 2012; 75(4):436-44. DOI: 10.1111/j.1365-3083.2012.02671.x. View

Blair P, Norena L, Flores-Borja F, Rawlings D, Isenberg D, Ehrenstein M . CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity. 2010; 32(1):129-40. DOI: 10.1016/j.immuni.2009.11.009. View

Sarvaria A, Basar R, Mehta R, Shaim H, Muftuoglu M, Khoder A . IL-10+ regulatory B cells are enriched in cord blood and may protect against cGVHD after cord blood transplantation. Blood. 2016; 128(10):1346-61. PMC: 5016705. DOI: 10.1182/blood-2016-01-695122. View

Mauri C, Ehrenstein M . The 'short' history of regulatory B cells. Trends Immunol. 2008; 29(1):34-40. DOI: 10.1016/j.it.2007.10.004. View

Kessel A, Haj T, Peri R, Snir A, Melamed D, Sabo E . Human CD19(+)CD25(high) B regulatory cells suppress proliferation of CD4(+) T cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells. Autoimmun Rev. 2011; 11(9):670-7. DOI: 10.1016/j.autrev.2011.11.018. View

Schatorje E, Gemen E, Driessen G, Leuvenink J, van Hout R, van der Burg M . Age-matched reference values for B-lymphocyte subpopulations and CVID classifications in children. Scand J Immunol. 2011; 74(5):502-10. DOI: 10.1111/j.1365-3083.2011.02609.x. View

Cerutti A, Cols M, Puga I . Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol. 2013; 13(2):118-32. PMC: 3652659. DOI: 10.1038/nri3383. View

Power L, Popplewell E, Holloway J, Diaper N, Warner J, Jones C . Immunoregulatory molecules during pregnancy and at birth. J Reprod Immunol. 2002; 56(1-2):19-28. DOI: 10.1016/s0165-0378(01)00146-2. View

10.

Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein M, Isenberg D . CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med. 2013; 5(173):173ra23. DOI: 10.1126/scitranslmed.3005407. View

11.

Sims G, Ettinger R, Shirota Y, Yarboro C, Illei G, Lipsky P . Identification and characterization of circulating human transitional B cells. Blood. 2005; 105(11):4390-8. PMC: 1895038. DOI: 10.1182/blood-2004-11-4284. View

12.

Matsushita T, Horikawa M, Iwata Y, Tedder T . Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. J Immunol. 2010; 185(4):2240-52. PMC: 3717968. DOI: 10.4049/jimmunol.1001307. View

13.

Veen W, Stanic B, Yaman G, Wawrzyniak M, Sollner S, Akdis D . IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013; 131(4):1204-12. DOI: 10.1016/j.jaci.2013.01.014. View

14.

Ruggeri A, Paviglianiti A, Gluckman E, Rocha V . Impact of HLA in cord blood transplantation outcomes. HLA. 2016; 87(6):413-21. DOI: 10.1111/tan.12792. View

15.

Allman D, Pillai S . Peripheral B cell subsets. Curr Opin Immunol. 2008; 20(2):149-57. PMC: 2532490. DOI: 10.1016/j.coi.2008.03.014. View

16.

Burdin N, Rousset F, Banchereau J . B-cell-derived IL-10: production and function. Methods. 1997; 11(1):98-111. DOI: 10.1006/meth.1996.0393. View

17.

Muzzio D, Zygmunt M, Jensen F . The role of pregnancy-associated hormones in the development and function of regulatory B cells. Front Endocrinol (Lausanne). 2014; 5:39. PMC: 3978254. DOI: 10.3389/fendo.2014.00039. View

18.

Goode I, Xu H, Ildstad S . Regulatory B cells: the new "it" cell. Transplant Proc. 2013; 46(1):3-8. DOI: 10.1016/j.transproceed.2013.08.075. View

19.

Chirumbolo S, Ortolani R, Veneri D, Raffaelli R, Peroni D, Pigozzi R . Lymphocyte phenotypic subsets in umbilical cord blood compared to peripheral blood from related mothers. Cytometry B Clin Cytom. 2011; 80(4):248-53. DOI: 10.1002/cyto.b.20588. View

20.

Jensen F, Muzzio D, Soldati R, Fest S, Zenclussen A . Regulatory B10 cells restore pregnancy tolerance in a mouse model. Biol Reprod. 2013; 89(4):90. DOI: 10.1095/biolreprod.113.110791. View