Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood - 06/06/18
on behalf of the
EuroFlow PID group
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 IgG1, IgG2, IgG3, IgA1, and IgA2 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 (IgG1, IgG3, and IgA1) peaked later during childhood (2-4 years), whereas MBCs expressing third IGHC gene block immunoglobulin isotypes (IgG2, IgG4, and IgA2) reached maximum values during adulthood. PCs were already detected in newborns, increasing in number until 6 to 11 months for IgM, IgG1, IgG2, IgG3, IgA1, and IgA2; until 2 to 4 years for IgD; and until 5 to 9 years for IgG4 and decreasing thereafter. For most IgH isotypes (except IgD and IgG4), 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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Immunoglobulins, IgH isotype, subclass, memory B cells, plasma cells, flow cytometry, reference ranges, normal B cells, age-related values
Abbreviations used : BM, CB, IgH, IGHC, MBC, PB, PC, RT, sm, SSC
Plan
| E.B. was supported by a grant from Junta de Castilla y León (Fondo Social Europeo, ORDEN EDU/346/2013, Valladolid, Spain). This work was supported by the CB16/12/00400 grant (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain, and FONDOS FEDER) and the FIS PI12/00905-FEDER grant from the Fondo de Investigaciones Sanitarias of Instituto de Salud Carlos III (Madrid, Spain). O.P. and T.K. were supported by the Ministry of Education, Youth and Sports (NPU I no. LO1604 and 15-28541A). The coordination and innovation processes of this study were supported by the EuroFlow Consortium. |
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| Disclosure of potential conflict of interest: E. Blanco, M. Pérez-Andrés, E. López-Granados, T. Kalina, M. van Zelm, M. van der Burg, J. J. M. van Dongen, and A. Orfao each report being one of the inventors on the EuroFlow-owned patent PCT/NL 2015/050762 (Diagnosis of primary immunodeficiencies), which is licensed to Cytognos, a company that pays royalties to the EuroFlow Consortium. M. van Zelm reports grants from the NHMRC and has a patent issued (EP 2780711 B1). J. J. M. van Dongen and A. Orfao report an Educational Services Agreement from BD Biosciences The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 6
P. 2208 - juin 2018 Retour au numéro
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