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

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): 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
BackgroundHumoral 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 (MBCs) and plasma cell (PCs) compartments remains to be investigated.ObjectiveWe studied the age-related distribution of MBCs and PCs expressing different IgH-isotypes, in addition to the immature/transitional and naive B-cell compartments.MethodsB-cell and PC subsets, and plasma IgH-isotype levels, were studied in cord blood (CB, n=19) and peripheral blood (n=215) from healthy donors aged 0-90y by flowcytometry and nephelometry, respectively.ResultsIgH-switched MBCs expressing IgG1,2,3 and IgA1,2 were already detected in CB and newborns at very low counts, while CD27⁺ IgM⁺⁺D⁺ MBCs only became detectable at 1-5months(m), remaining stable until 2-4y, and IgD MBCs peaked at 2-4y, both populations decreasing thereafter. MBCs expressing IgH-isotypes of the second IGH-constant (IGHC) gene-block (IgG1, IgG3 and IgA1) peaked later during childhood (2-4y), while MBCs expressing third IGHC gene-block Ig-isotypes (IgG2, IgG4 and IgA2) reached their maximum during adulthood. PCs were already detected in newborns, increasing until 6-11m for IgM, IgG1-3 and IgA1-2, until 2-4y for IgD and until 5-9y for IgG4, decreasing thereafter. For most IgH-isotypes (except IgD and IgG4), maximum plasma levels were reached after PCs and MBCs peaked.ConclusionsPCs reach maximum values early in life, followed by MBCs 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.

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