Characterization of Early Activation Events in Cord Blood B Cells after Stimulation with T Cell-Independent Activators

Abstract

Human neonates are immunologically immature, particularly in their humoral antibody responses to T cell-independent antigens, as exemplified by their increased susceptibility to infections with polysaccharide-encapsulated bacteria. To clarify the mechanism(s) underlying the unresponsiveness of neonates to polysaccharide antigens, we used an in vitro model with neonatal cord blood cells that has been shown to mimic surface Ig-dependent signaling in the adult by T cell-independent antigens. We studied the ability of cord blood human B cells to become activated after ligation of their surface Ig by unconjugated anti-Ig, dextran-conjugated anti-Ig, and Staphylococcus aureus Cowan A1, and compared their response with that of adult B cells. After the addition of nanogram concentrations of anti-Ig-dextran, neonatal cord blood B cells proliferated at levels comparable to that observed with adult B cells. The majority of cord blood B cells showed a marked rise in intracellular calcium, increased surface expression of human leukocyte antigen DR, and an increase in cell size. Direct activation of protein kinase C by phorbol esters in neonatal B cells led to cellular proliferation, and when combined with anti-Ig, a synergistic effect on proliferation was observed. These data suggest that the unresponsiveness of human neonates to polysaccharide antigens does not represent an inability of these antigens to induce early activation events in circulating B cells.

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

“…35,64 Further expansion of CD27 1 MBCs during the first year of life occurred in parallel with an increased proportion of CD21 2 (C3d receptor) MBCs with a limited ability to respond to polysaccharide-complement complexes. 65,66 The fact that within naive B cells the percentage of CD21 2 cells remains stable with age and shows a comparable in vitro response to polysaccharide antigens in children and adults 67 suggests that external factors affecting antigen recognition might increase the production of C3d receptor-deficient MBCs in children of around 1 year of age when serum C3 levels reach adult-like values. 68 Thus the limited availability of C3d and C3d-antigen complexes in infants less than 1 year old because low serum C3 levels 69 might contribute to reduced signaling for expression of this receptor during antigen recognition.…”

B-cell–T-cell activation and interaction in common variable immunodeficiency

“…␣-␦-dex consists of high-molecular-weight dextran polysaccharide carrier molecules, which are coupled to polyclonal anti-IgD antibodies that can induce a multivalent stimulus to B cells [26,27]. The concentration of ␣-␦-dex [26,28] used was 1 g/ml.…”

Functional responses of human neonatal B lymphocytes to antigen receptor cross-linking and CpG DNA

“…In particular, while ligation of the B cell antigen receptor (BCR) induces MHC Class II up‐regulation and proliferation in mature adult B cells, neonatal B cells fail to hyperexpress MHC class II [11] and are induced to undergo apoptosis by this stimulus [12]. In contrast to these murine studies, some authors have shown that human cord blood B cells can respond positively to cross‐linking of the antigen receptor [13–15].…”