Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood

Elena Blanco, Martín Pérez-Andrés, Sonia Arriba-Méndez, Teresa Contreras-Sanfeliciano, Ignacio Criado, Ondrej Pelak, Ana Serra-Caetano, Alfonso Romero, Noemí Puig, Ana Remesal, Juan Torres Canizales, Eduardo López-Granados, Tomas Kalina, Ana E. Sousa, Menno van Zelm, Mirjam van der Burg, Jacques J.M. van Dongen, Alberto Orfao, on behalf of the EuroFlow PID group

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15 Citations (Scopus)

Abstract

Background: Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity, and neoplasia. Immunoglobulin heavy chain (IgH) isotype serum levels can partly explain such age-related differences, but their relationship with the IgH isotype distribution within memory B-cell (MBC) and plasma cell (PCs) compartments remains to be investigated. Objective: We studied the age-related distribution of MBCs and PCs expressing different IgH isotypes in addition to the immature/transitional and naive B-cell compartments. Methods: B-cell and PC subsets and plasma IgH isotype levels were studied in cord blood (n = 19) and peripheral blood (n = 215) from healthy donors aged 0 to 90 years by using flow cytometry and nephelometry, respectively. Results: IgH-switched MBCs expressing IgG 1 , IgG 2 , IgG 3 , IgA 1 , and IgA 2 were already detected in cord blood and newborns at very low counts, whereas CD27 + IgM ++ IgD + MBCs only became detectable at 1 to 5 months and remained stable until 2 to 4 years, and IgD MBCs peaked at 2 to 4 years, with both populations decreasing thereafter. MBCs expressing IgH isotypes of the second immunoglobulin heavy chain constant region (IGHC) gene block (IgG 1 , IgG 3 , and IgA 1 ) peaked later during childhood (2-4 years), whereas MBCs expressing third IGHC gene block immunoglobulin isotypes (IgG 2 , IgG 4 , and IgA 2 ) reached maximum values during adulthood. PCs were already detected in newborns, increasing in number until 6 to 11 months for IgM, IgG 1 , IgG 2 , IgG 3 , IgA 1 , and IgA 2 ; until 2 to 4 years for IgD; and until 5 to 9 years for IgG 4 and decreasing thereafter. For most IgH isotypes (except IgD and IgG 4 ), maximum plasma levels were reached after PC and MBC counts peaked. Conclusions: PC counts reach maximum values early in life, followed by MBC counts and plasma IgH isotypes. Importantly, IgH isotypes from different IGHC gene blocks show different patterns, probably reflecting consecutive cycles of IgH isotype switch recombination through life.

Original languageEnglish
Pages (from-to)2208-2219.e16
Number of pages28
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • age-related values
  • flow cytometry
  • IgH isotype
  • Immunoglobulins
  • memory B cells
  • normal B cells
  • plasma cells
  • reference ranges
  • subclass

Cite this

Blanco, E., Pérez-Andrés, M., Arriba-Méndez, S., Contreras-Sanfeliciano, T., Criado, I., Pelak, O., ... on behalf of the EuroFlow PID group (2018). Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood. Journal of Allergy and Clinical Immunology, 141(6), 2208-2219.e16. https://doi.org/10.1016/j.jaci.2018.02.017
Blanco, Elena ; Pérez-Andrés, Martín ; Arriba-Méndez, Sonia ; Contreras-Sanfeliciano, Teresa ; Criado, Ignacio ; Pelak, Ondrej ; Serra-Caetano, Ana ; Romero, Alfonso ; Puig, Noemí ; Remesal, Ana ; Torres Canizales, Juan ; López-Granados, Eduardo ; Kalina, Tomas ; Sousa, Ana E. ; van Zelm, Menno ; van der Burg, Mirjam ; van Dongen, Jacques J.M. ; Orfao, Alberto ; on behalf of the EuroFlow PID group. / Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood. In: Journal of Allergy and Clinical Immunology. 2018 ; Vol. 141, No. 6. pp. 2208-2219.e16.
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abstract = "Background: Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity, and neoplasia. Immunoglobulin heavy chain (IgH) isotype serum levels can partly explain such age-related differences, but their relationship with the IgH isotype distribution within memory B-cell (MBC) and plasma cell (PCs) compartments remains to be investigated. Objective: We studied the age-related distribution of MBCs and PCs expressing different IgH isotypes in addition to the immature/transitional and naive B-cell compartments. Methods: B-cell and PC subsets and plasma IgH isotype levels were studied in cord blood (n = 19) and peripheral blood (n = 215) from healthy donors aged 0 to 90 years by using flow cytometry and nephelometry, respectively. Results: IgH-switched MBCs expressing IgG 1 , IgG 2 , IgG 3 , IgA 1 , and IgA 2 were already detected in cord blood and newborns at very low counts, whereas CD27 + IgM ++ IgD + MBCs only became detectable at 1 to 5 months and remained stable until 2 to 4 years, and IgD MBCs peaked at 2 to 4 years, with both populations decreasing thereafter. MBCs expressing IgH isotypes of the second immunoglobulin heavy chain constant region (IGHC) gene block (IgG 1 , IgG 3 , and IgA 1 ) peaked later during childhood (2-4 years), whereas MBCs expressing third IGHC gene block immunoglobulin isotypes (IgG 2 , IgG 4 , and IgA 2 ) reached maximum values during adulthood. PCs were already detected in newborns, increasing in number until 6 to 11 months for IgM, IgG 1 , IgG 2 , IgG 3 , IgA 1 , and IgA 2 ; until 2 to 4 years for IgD; and until 5 to 9 years for IgG 4 and decreasing thereafter. For most IgH isotypes (except IgD and IgG 4 ), maximum plasma levels were reached after PC and MBC counts peaked. Conclusions: PC counts reach maximum values early in life, followed by MBC counts and plasma IgH isotypes. Importantly, IgH isotypes from different IGHC gene blocks show different patterns, probably reflecting consecutive cycles of IgH isotype switch recombination through life.",
keywords = "age-related values, flow cytometry, IgH isotype, Immunoglobulins, memory B cells, normal B cells, plasma cells, reference ranges, subclass",
author = "Elena Blanco and Mart{\'i}n P{\'e}rez-Andr{\'e}s and Sonia Arriba-M{\'e}ndez and Teresa Contreras-Sanfeliciano and Ignacio Criado and Ondrej Pelak and Ana Serra-Caetano and Alfonso Romero and Noem{\'i} Puig and Ana Remesal and {Torres Canizales}, Juan and Eduardo L{\'o}pez-Granados and Tomas Kalina and Sousa, {Ana E.} and {van Zelm}, Menno and {van der Burg}, Mirjam and {van Dongen}, {Jacques J.M.} and Alberto Orfao and {on behalf of the EuroFlow PID group}",
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Blanco, E, Pérez-Andrés, M, Arriba-Méndez, S, Contreras-Sanfeliciano, T, Criado, I, Pelak, O, Serra-Caetano, A, Romero, A, Puig, N, Remesal, A, Torres Canizales, J, López-Granados, E, Kalina, T, Sousa, AE, van Zelm, M, van der Burg, M, van Dongen, JJM, Orfao, A & on behalf of the EuroFlow PID group 2018, 'Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood', Journal of Allergy and Clinical Immunology, vol. 141, no. 6, pp. 2208-2219.e16. https://doi.org/10.1016/j.jaci.2018.02.017

Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood. / Blanco, Elena; Pérez-Andrés, Martín; Arriba-Méndez, Sonia; Contreras-Sanfeliciano, Teresa; Criado, Ignacio; Pelak, Ondrej; Serra-Caetano, Ana; Romero, Alfonso; Puig, Noemí; Remesal, Ana; Torres Canizales, Juan; López-Granados, Eduardo; Kalina, Tomas; Sousa, Ana E.; van Zelm, Menno; van der Burg, Mirjam; van Dongen, Jacques J.M.; Orfao, Alberto; on behalf of the EuroFlow PID group.

In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 6, 01.06.2018, p. 2208-2219.e16.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood

AU - Blanco, Elena

AU - Pérez-Andrés, Martín

AU - Arriba-Méndez, Sonia

AU - Contreras-Sanfeliciano, Teresa

AU - Criado, Ignacio

AU - Pelak, Ondrej

AU - Serra-Caetano, Ana

AU - Romero, Alfonso

AU - Puig, Noemí

AU - Remesal, Ana

AU - Torres Canizales, Juan

AU - López-Granados, Eduardo

AU - Kalina, Tomas

AU - Sousa, Ana E.

AU - van Zelm, Menno

AU - van der Burg, Mirjam

AU - van Dongen, Jacques J.M.

AU - Orfao, Alberto

AU - on behalf of the EuroFlow PID group

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background: Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity, and neoplasia. Immunoglobulin heavy chain (IgH) isotype serum levels can partly explain such age-related differences, but their relationship with the IgH isotype distribution within memory B-cell (MBC) and plasma cell (PCs) compartments remains to be investigated. Objective: We studied the age-related distribution of MBCs and PCs expressing different IgH isotypes in addition to the immature/transitional and naive B-cell compartments. Methods: B-cell and PC subsets and plasma IgH isotype levels were studied in cord blood (n = 19) and peripheral blood (n = 215) from healthy donors aged 0 to 90 years by using flow cytometry and nephelometry, respectively. Results: IgH-switched MBCs expressing IgG 1 , IgG 2 , IgG 3 , IgA 1 , and IgA 2 were already detected in cord blood and newborns at very low counts, whereas CD27 + IgM ++ IgD + MBCs only became detectable at 1 to 5 months and remained stable until 2 to 4 years, and IgD MBCs peaked at 2 to 4 years, with both populations decreasing thereafter. MBCs expressing IgH isotypes of the second immunoglobulin heavy chain constant region (IGHC) gene block (IgG 1 , IgG 3 , and IgA 1 ) peaked later during childhood (2-4 years), whereas MBCs expressing third IGHC gene block immunoglobulin isotypes (IgG 2 , IgG 4 , and IgA 2 ) reached maximum values during adulthood. PCs were already detected in newborns, increasing in number until 6 to 11 months for IgM, IgG 1 , IgG 2 , IgG 3 , IgA 1 , and IgA 2 ; until 2 to 4 years for IgD; and until 5 to 9 years for IgG 4 and decreasing thereafter. For most IgH isotypes (except IgD and IgG 4 ), maximum plasma levels were reached after PC and MBC counts peaked. Conclusions: PC counts reach maximum values early in life, followed by MBC counts and plasma IgH isotypes. Importantly, IgH isotypes from different IGHC gene blocks show different patterns, probably reflecting consecutive cycles of IgH isotype switch recombination through life.

AB - Background: Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity, and neoplasia. Immunoglobulin heavy chain (IgH) isotype serum levels can partly explain such age-related differences, but their relationship with the IgH isotype distribution within memory B-cell (MBC) and plasma cell (PCs) compartments remains to be investigated. Objective: We studied the age-related distribution of MBCs and PCs expressing different IgH isotypes in addition to the immature/transitional and naive B-cell compartments. Methods: B-cell and PC subsets and plasma IgH isotype levels were studied in cord blood (n = 19) and peripheral blood (n = 215) from healthy donors aged 0 to 90 years by using flow cytometry and nephelometry, respectively. Results: IgH-switched MBCs expressing IgG 1 , IgG 2 , IgG 3 , IgA 1 , and IgA 2 were already detected in cord blood and newborns at very low counts, whereas CD27 + IgM ++ IgD + MBCs only became detectable at 1 to 5 months and remained stable until 2 to 4 years, and IgD MBCs peaked at 2 to 4 years, with both populations decreasing thereafter. MBCs expressing IgH isotypes of the second immunoglobulin heavy chain constant region (IGHC) gene block (IgG 1 , IgG 3 , and IgA 1 ) peaked later during childhood (2-4 years), whereas MBCs expressing third IGHC gene block immunoglobulin isotypes (IgG 2 , IgG 4 , and IgA 2 ) reached maximum values during adulthood. PCs were already detected in newborns, increasing in number until 6 to 11 months for IgM, IgG 1 , IgG 2 , IgG 3 , IgA 1 , and IgA 2 ; until 2 to 4 years for IgD; and until 5 to 9 years for IgG 4 and decreasing thereafter. For most IgH isotypes (except IgD and IgG 4 ), maximum plasma levels were reached after PC and MBC counts peaked. Conclusions: PC counts reach maximum values early in life, followed by MBC counts and plasma IgH isotypes. Importantly, IgH isotypes from different IGHC gene blocks show different patterns, probably reflecting consecutive cycles of IgH isotype switch recombination through life.

KW - age-related values

KW - flow cytometry

KW - IgH isotype

KW - Immunoglobulins

KW - memory B cells

KW - normal B cells

KW - plasma cells

KW - reference ranges

KW - subclass

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U2 - 10.1016/j.jaci.2018.02.017

DO - 10.1016/j.jaci.2018.02.017

M3 - Article

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JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

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Blanco E, Pérez-Andrés M, Arriba-Méndez S, Contreras-Sanfeliciano T, Criado I, Pelak O et al. Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood. Journal of Allergy and Clinical Immunology. 2018 Jun 1;141(6):2208-2219.e16. https://doi.org/10.1016/j.jaci.2018.02.017