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B-cell subpopulations in children: National reference values.

Duchamp M, Sterlin D, Diabate A, Uring-Lambert B, Guérin-El Khourouj V, Le Mauff B, Monnier D, Malcus C, Labalette M, Picard C - Immun Inflamm Dis (2014)

Bottom Line: We found that the naive B-cells percentage declined between the ages of 6 months and 8 years, after which it remained stable at about 70-80%.The definition of reference intervals for pediatric B-cell levels should facilitate the screening and diagnosis of various B-cell immunodeficiencies.This multicenter study, providing national reference values, should thus facilitate immunological diagnosis in children.

View Article: PubMed Central - PubMed

Affiliation: Study Center of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (APHP), Necker Hospital Paris, France.

ABSTRACT
Peripheral B-lymphocytes undergo a series of changes during the first few years of life. Encounters with foreign antigens lead to maturation and differentiation. Several primary antibody deficiencies (PADs) affecting B-cell development are associated with abnormalities in the composition and/or differentiation of B-cell compartments. The most recent international classifications of primary immunodeficiencies (PIDs) and common variable immunodeficiencies (CVID) have highlighted the importance of B-cell immunophenotyping and age-specific reference intervals for diagnostic purposes. We established national reference values for memory B-cell subpopulations, on the basis of CD27 and surface IgD expression in the peripheral blood of 242 healthy children. We report here the absolute counts and percentages of naive, switched and non-switched memory B-cells for seven age groups, from neonates to adults. We found that the naive B-cells percentage declined between the ages of 6 months and 8 years, after which it remained stable at about 70-80%. Memory B-cells are already present at birth and their numbers increase throughout childhood, stabilizing between the ages of 12 and 18 years. The definition of reference intervals for pediatric B-cell levels should facilitate the screening and diagnosis of various B-cell immunodeficiencies. This multicenter study, providing national reference values, should thus facilitate immunological diagnosis in children.

No MeSH data available.


Related in: MedlinePlus

Changes in the percentage (A) and absolute number (B) of total B-cells with age. The proportions of lymphocytes accounted for by total B-cells (CD19+) (A) were analyzed by flow cytometry on whole-blood samples. The corresponding absolute numbers (B) were calculated from the absolute numbers of lymphocytes. Solid horizontal lines indicate the median values for each age group. m = month; y = year.
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fig02: Changes in the percentage (A) and absolute number (B) of total B-cells with age. The proportions of lymphocytes accounted for by total B-cells (CD19+) (A) were analyzed by flow cytometry on whole-blood samples. The corresponding absolute numbers (B) were calculated from the absolute numbers of lymphocytes. Solid horizontal lines indicate the median values for each age group. m = month; y = year.

Mentions: We initially included 292 children, but 50 of these children were excluded according to the Dixon's rule for non-Gaussian populations. B-cell subpopulations were therefore studied in a final population of 242. These children were classified into seven groups on the basis of age: from birth to 1 month of age (n = 14), from 1 to 6 months (n = 19), from 6 to 18 months (n = 37), from 18 months to 4 years (n = 37), from 4 to 8 years (n = 36), from 8 to 12 years (n = 36) and from 12 to 18 years (n = 63; Table1). During the first few days of life, B-cell percentage and counts were very low (Fig. 2). Given the relative lymphocytosis observed in infants, the absolute number of B-cells was high between the ages of 1 month and 18 months. It subsequently decreased (Fig. 2B), whereas the percentage of B-cells remained more or less stable after the age of 18 months (Fig. 2A). Naive B-cells continue to express IgD at the cell surface, but they do not yet display CD27 expression, which is induced by antigen-receptor activation in B-cells. There was a significant, large increase in the size of the naive B-cell pool during the first 6 months of life (P < 0.0001 for comparison of the 0–1 and 1–6 months age groups), due to the physiological lymphocytosis in infants, but the percentage of naive B-cells among total B-cells was similar for the 0–1 and 1–6 months age groups (P = 0.61) (Tables2 and 3, Fig. 3). The percentage of naive B-cells among total B-cells decreased steadily from birth to the age of 12 years. The 1–6 months and 6–18 months age groups displayed the largest decrease in naive B-cell percentage (P < 0.0001), and further decreases were observed in the 6–18 months and 18 months to 4 years age groups (P < 0.0001). Further slight but significant decreases were observed in the 18 months to 4 years and 4–8 years age groups (P = 0.04), followed by a stabilization of naive B-cell percentage at about 70–80%. The apparent slight increase observed in the 12–18 years age group was not significant (P = 0.1; Fig. 2A). The absolute number of naive B-cells increased during the first month of life to reach a steady state that was maintained until the age of 18 months, with no significant difference between the values obtained between the ages of 1 month and 18 months (P = 0.9). The subsequent rapid decrease in the number of naive B-cells reflects a physiological decrease in the size of the lymphocyte and B-cell populations on one hand, and a decrease in the percentage of naive B-cells on the other. Finally, despite the considerable dispersion of naive B-cell percentage values, particularly for children under the age of 4 years, absolute naive B-cell counts eventually stabilized at about 250 cells per microliter of blood, with lower levels of inter-individual variability (Fig. 3B).


B-cell subpopulations in children: National reference values.

Duchamp M, Sterlin D, Diabate A, Uring-Lambert B, Guérin-El Khourouj V, Le Mauff B, Monnier D, Malcus C, Labalette M, Picard C - Immun Inflamm Dis (2014)

Changes in the percentage (A) and absolute number (B) of total B-cells with age. The proportions of lymphocytes accounted for by total B-cells (CD19+) (A) were analyzed by flow cytometry on whole-blood samples. The corresponding absolute numbers (B) were calculated from the absolute numbers of lymphocytes. Solid horizontal lines indicate the median values for each age group. m = month; y = year.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4257758&req=5

fig02: Changes in the percentage (A) and absolute number (B) of total B-cells with age. The proportions of lymphocytes accounted for by total B-cells (CD19+) (A) were analyzed by flow cytometry on whole-blood samples. The corresponding absolute numbers (B) were calculated from the absolute numbers of lymphocytes. Solid horizontal lines indicate the median values for each age group. m = month; y = year.
Mentions: We initially included 292 children, but 50 of these children were excluded according to the Dixon's rule for non-Gaussian populations. B-cell subpopulations were therefore studied in a final population of 242. These children were classified into seven groups on the basis of age: from birth to 1 month of age (n = 14), from 1 to 6 months (n = 19), from 6 to 18 months (n = 37), from 18 months to 4 years (n = 37), from 4 to 8 years (n = 36), from 8 to 12 years (n = 36) and from 12 to 18 years (n = 63; Table1). During the first few days of life, B-cell percentage and counts were very low (Fig. 2). Given the relative lymphocytosis observed in infants, the absolute number of B-cells was high between the ages of 1 month and 18 months. It subsequently decreased (Fig. 2B), whereas the percentage of B-cells remained more or less stable after the age of 18 months (Fig. 2A). Naive B-cells continue to express IgD at the cell surface, but they do not yet display CD27 expression, which is induced by antigen-receptor activation in B-cells. There was a significant, large increase in the size of the naive B-cell pool during the first 6 months of life (P < 0.0001 for comparison of the 0–1 and 1–6 months age groups), due to the physiological lymphocytosis in infants, but the percentage of naive B-cells among total B-cells was similar for the 0–1 and 1–6 months age groups (P = 0.61) (Tables2 and 3, Fig. 3). The percentage of naive B-cells among total B-cells decreased steadily from birth to the age of 12 years. The 1–6 months and 6–18 months age groups displayed the largest decrease in naive B-cell percentage (P < 0.0001), and further decreases were observed in the 6–18 months and 18 months to 4 years age groups (P < 0.0001). Further slight but significant decreases were observed in the 18 months to 4 years and 4–8 years age groups (P = 0.04), followed by a stabilization of naive B-cell percentage at about 70–80%. The apparent slight increase observed in the 12–18 years age group was not significant (P = 0.1; Fig. 2A). The absolute number of naive B-cells increased during the first month of life to reach a steady state that was maintained until the age of 18 months, with no significant difference between the values obtained between the ages of 1 month and 18 months (P = 0.9). The subsequent rapid decrease in the number of naive B-cells reflects a physiological decrease in the size of the lymphocyte and B-cell populations on one hand, and a decrease in the percentage of naive B-cells on the other. Finally, despite the considerable dispersion of naive B-cell percentage values, particularly for children under the age of 4 years, absolute naive B-cell counts eventually stabilized at about 250 cells per microliter of blood, with lower levels of inter-individual variability (Fig. 3B).

Bottom Line: We found that the naive B-cells percentage declined between the ages of 6 months and 8 years, after which it remained stable at about 70-80%.The definition of reference intervals for pediatric B-cell levels should facilitate the screening and diagnosis of various B-cell immunodeficiencies.This multicenter study, providing national reference values, should thus facilitate immunological diagnosis in children.

View Article: PubMed Central - PubMed

Affiliation: Study Center of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris (APHP), Necker Hospital Paris, France.

ABSTRACT
Peripheral B-lymphocytes undergo a series of changes during the first few years of life. Encounters with foreign antigens lead to maturation and differentiation. Several primary antibody deficiencies (PADs) affecting B-cell development are associated with abnormalities in the composition and/or differentiation of B-cell compartments. The most recent international classifications of primary immunodeficiencies (PIDs) and common variable immunodeficiencies (CVID) have highlighted the importance of B-cell immunophenotyping and age-specific reference intervals for diagnostic purposes. We established national reference values for memory B-cell subpopulations, on the basis of CD27 and surface IgD expression in the peripheral blood of 242 healthy children. We report here the absolute counts and percentages of naive, switched and non-switched memory B-cells for seven age groups, from neonates to adults. We found that the naive B-cells percentage declined between the ages of 6 months and 8 years, after which it remained stable at about 70-80%. Memory B-cells are already present at birth and their numbers increase throughout childhood, stabilizing between the ages of 12 and 18 years. The definition of reference intervals for pediatric B-cell levels should facilitate the screening and diagnosis of various B-cell immunodeficiencies. This multicenter study, providing national reference values, should thus facilitate immunological diagnosis in children.

No MeSH data available.


Related in: MedlinePlus