Plasma Cell Differentiation and Immunoglobulin Secretion Are Induced by lnterleukin-4 and Anti-CD40 and Differ in Cord Blood and Adult Naive B-Cells

摘要

Background: Cord blood (CB) B-cells produce low amounts of antibodies indicating immaturity of the cells or the environment they reside in. Our aim was to investigate class switch recombination and plasma cell differentiation to IgE and IgG_4 in IgD~+ B-cells from CB in comparison to adult peripheral blood (PB). Methods: IgD~+ B-cells from CB and PB were stimulated with IL-4 and anti-CD40. After 4 or 12 days of stimulation, germline transcripts (GLTs), AID, XBP-1, CD38, CD 138, intracellular IgE and XBP-J and secreted immunoglobulins were measured. Results: After 4 days of stimulation, epsilon and gamma4 GLTs were induced in both CB and PB B-cells. No significant differences were observed in the levels of AID between the two groups. After 12 days of stimulation, secretion of IgE and IgG_4 were induced to a similar level in both groups whereas IgG were only significantly upregu-lated in CB-cells. Both groups displayed a low but detectable IgA. The plasma cell markers CD38 and CD 138 were highly uprcgulated in stimulated CB-cells compared to stimulated PB-cells whereas XBP-1 was expressed at a similar level in the two groups. Conclusion: IL-4 and CD40-ligation increased the secretion of IgE and IgG_4 in both CB and PB B-cells. Thus naive CB B-cclls can easily be affected to switch to IgE and IgG_4, but are more easily further differentiated to become IgE but not IgG_4 producing plasma cells compared to PB-cells.