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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 memory B-cells with age. The proportions of total memory B-cells (CD27+) (A) among CD19+ lymphocytes were analyzed by flow cytometry on whole-blood samples. The corresponding absolute numbers (B) were calculated from the absolute number of B-cells. Solid horizontal lines indicate the median values for each age group. m = month; y = year.
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fig04: Changes in the percentage (A) and absolute number (B) of total memory B-cells with age. The proportions of total memory B-cells (CD27+) (A) among CD19+ lymphocytes were analyzed by flow cytometry on whole-blood samples. The corresponding absolute numbers (B) were calculated from the absolute number of B-cells. Solid horizontal lines indicate the median values for each age group. m = month; y = year.

Mentions: We analyzed the age-dependent distribution of the various mature peripheral B-cell subsets by double-labeling for CD27 and IgD. Surface CD27 expression defines memory B-cells, a population comprising two different subsets: non-switched memory B-cells or marginal zone B-cells, which continue to express IgD on their surface (CD19+ CD27+ IgD+) and switched memory B-cells, which are characterized by a loss of IgD expression (CD19+ CD27+ IgD−). The proportion of total memory B-cells (corresponding to both subsets; Fig. 4A) gradually increased, reaching a peak between the ages of 4 and 8 years (median: 18.4%, Table2), whereas the absolute count of CD27+ B-cells peaked between the ages of 6 months and 4 years, subsequently decreasing and then stabilizing (Fig. 4B, Table2). The percentage of non-switched and switched memory B-cells among total B-cells increased during infancy, but with different time courses (Table2, Fig. 5A and C). Switched memory B-cells were almost undetectable between birth and the age of 6 months, whereas non-switched memory B-cells were already present, albeit at very low percentages, in the first 6 months of life. We also observed a gradual slight increase in the percentage of CD27+ IgD+ B-cells, whereas the percentage of CD27+ IgD− B-cells increased more rapidly between the 6–18 months and 18 months to 4 years age groups, reaching a peak at the age of 8–12 years before stabilizing. We also observed differences in absolute numbers between these two subsets of memory B-cells (Table3, Fig. 5B and D). During the increase in total B-cell numbers between 1–6 months and 18 months to 4 years, the absolute numbers of non-switched memory B-cells increased similarly and then decreased, but this decrease occurred later than that in the number of total B-cells. The decrease was highly significant for total B-cells between 6–18 months and 18 months to 4 years (P < 0.0001) whereas the decrease in the numbers of CD27+ IgD+ B-cells was not significant between 6–18 months and 18 months to 4 years (P = 0.32) but was significant between 18 months to 4 years and 4–8 years (P = 0.009). Conversely, the absolute number of switched memory B-cells gradually increased, peaking between the ages of 18 months and 4 years, but remaining stable thereafter, with no significant decrease. The large differences within age groups may be accounted for by variations in genetic background, antigen exposure, or environmental factors influencing B-cell maturation. However, it is important to have access to “normal” ranges of these values, to make it possible to identify children with an impaired B-cell phenotype.


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 memory B-cells with age. The proportions of total memory B-cells (CD27+) (A) among CD19+ lymphocytes were analyzed by flow cytometry on whole-blood samples. The corresponding absolute numbers (B) were calculated from the absolute number of B-cells. 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

fig04: Changes in the percentage (A) and absolute number (B) of total memory B-cells with age. The proportions of total memory B-cells (CD27+) (A) among CD19+ lymphocytes were analyzed by flow cytometry on whole-blood samples. The corresponding absolute numbers (B) were calculated from the absolute number of B-cells. Solid horizontal lines indicate the median values for each age group. m = month; y = year.
Mentions: We analyzed the age-dependent distribution of the various mature peripheral B-cell subsets by double-labeling for CD27 and IgD. Surface CD27 expression defines memory B-cells, a population comprising two different subsets: non-switched memory B-cells or marginal zone B-cells, which continue to express IgD on their surface (CD19+ CD27+ IgD+) and switched memory B-cells, which are characterized by a loss of IgD expression (CD19+ CD27+ IgD−). The proportion of total memory B-cells (corresponding to both subsets; Fig. 4A) gradually increased, reaching a peak between the ages of 4 and 8 years (median: 18.4%, Table2), whereas the absolute count of CD27+ B-cells peaked between the ages of 6 months and 4 years, subsequently decreasing and then stabilizing (Fig. 4B, Table2). The percentage of non-switched and switched memory B-cells among total B-cells increased during infancy, but with different time courses (Table2, Fig. 5A and C). Switched memory B-cells were almost undetectable between birth and the age of 6 months, whereas non-switched memory B-cells were already present, albeit at very low percentages, in the first 6 months of life. We also observed a gradual slight increase in the percentage of CD27+ IgD+ B-cells, whereas the percentage of CD27+ IgD− B-cells increased more rapidly between the 6–18 months and 18 months to 4 years age groups, reaching a peak at the age of 8–12 years before stabilizing. We also observed differences in absolute numbers between these two subsets of memory B-cells (Table3, Fig. 5B and D). During the increase in total B-cell numbers between 1–6 months and 18 months to 4 years, the absolute numbers of non-switched memory B-cells increased similarly and then decreased, but this decrease occurred later than that in the number of total B-cells. The decrease was highly significant for total B-cells between 6–18 months and 18 months to 4 years (P < 0.0001) whereas the decrease in the numbers of CD27+ IgD+ B-cells was not significant between 6–18 months and 18 months to 4 years (P = 0.32) but was significant between 18 months to 4 years and 4–8 years (P = 0.009). Conversely, the absolute number of switched memory B-cells gradually increased, peaking between the ages of 18 months and 4 years, but remaining stable thereafter, with no significant decrease. The large differences within age groups may be accounted for by variations in genetic background, antigen exposure, or environmental factors influencing B-cell maturation. However, it is important to have access to “normal” ranges of these values, to make it possible to identify children with an impaired B-cell phenotype.

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