A median of 2.6% (range 1.0–12.6%) of B-lymphocytes were TACI-positive. No correlation was found between switched memory B-lymphocyte numbers and the percentage of TACI+ B-lymphocytes (r = 0.213, P = 0.213); a negative correlation was found between naive B-lymphocyte numbers and the percentage of TACI+ B-lymphocytes (r = −0.738, P = 0.000),
and a positive correlation between the percentage of TACI+ B-lymphocytes and age (r = 0.538, P = 0.001). A partial correlation was computed controlling for age to investigate whether the negative correlation between the percentage of TACI+ B-lymphocytes and naive B-lymphocyte numbers was based on the developmental role of age only. After correction for age, the negative correlation between the percentage of TACI+
click here B-lymphocytes and naive B-lymphocyte numbers disappeared (r = -0.318, P = 0.063), CP-690550 in vitro showing that age is the primary determinant of TACI-expression on B-lymphocytes. The B-lymphocyte subpopulations used in the EUROclass CVID classification clearly show an age-related development during childhood. When our group of healthy children would be assessed according to the EUROclass classification, 40 out of 97 children would be classified in one of the subgroups due to the fact that they show lower relative numbers of switched memory B-lymphocytes (Fig. 2). Within this group 27 children showed high relative numbers of transitional B cells. However, 38 of these 40 children
were younger than two years of age, when the diagnosis of CVID cannot yet be made. B cell immunophenotyping characteristics correlate with clinical complications in adults with CVID and are therefore used for classification of patients; currently, the EUROclass classification is most commonly used [17]. We and others [18–26] demonstrate that the B-lymphocyte compartments of normal adults and children of various ages differ considerably, implicating that data Methane monooxygenase obtained in adults should not be extrapolated to children. These differences seem logical when looking at normal B cell development: after initial maturation in the bone marrow, the first cells to emigrate into the peripheral blood are transitional (CD19+CD38++IgM++) B cells and naive B-lymphocytes (CD19+CD27-IgM+IgD+) [29, 30]. The next step leads to short-lived antibody-secreting plasma cells, switched memory B-lymphocytes, or natural effector cells, depending on the environment during activation, and the presence or absence of help from T-lymphocytes [31–34]. These last steps are antigen dependent; they are also the steps that are disturbed in CVID. CD21low B-cells (CD19+CD21lowCD38low) are rare in the blood of healthy individuals but can be found in patients with autoimmune disease [35].
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