CHARACTERIZATION OF EARLY ACTIVATION EVENTS IN CORD-BLOOD B-CELLS AFTER STIMULATION WITH T-CELL-INDEPENDENT ACTIVATORS

Human neonates are immunologically immature, particularly in their hum oral antibody responses to T cell-independent antigens, as exemplified by their increased susceptibility to infections with polysaccharide-e ncapsulated bacteria. To clarify the mechanism(s) underlying the unres ponsiveness of neonates to polysaccharide antigens, we used an in vitr o model with neonatal cord blood cells that has been shown to mimic su rface Ig dependent signaling in the adult by T cell-independent antige ns. We studied the ability of cord blood human B cells to become activ ated after ligation of their surface Ig by unconjugated anti-Ig, dextr an-conjugated anti-Ig, and Staphylococcus aureus Cowan Al, and compare d their response with that of adult B cells. After the addition of nan ogram concentrations of anti-Ig-dextran, neonatal cord blood B cells p roliferated at levels comparable to that observed with adult B cells. The majority of cord blood B cells showed a marked rise in intracellul ar calcium, increased surface expression of human leukoctyte antigen D R, 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 ne onates to polysaccharide antigens does not represent an inability of t hese antigens to induce early activation events in circulating B cells .