Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4+ T cell subset expressing homing receptor L-selectin.

Abstract

The humoral response in newborns is mainly restricted to IgM production, which may be attributable to the naive nature of both B and T cells at birth. In light of the current evidence that memory (CD45RO+) CD4+ T cells help B cell differentiation, the present study was undertaken to examine whether a specified population within memory CD4+ T cells could induce the maturation of neonatal naive B cells. In the conventional PWM-stimulated cultures, the generation of IgG- and IgA-producing cells in addition to IgM production by neonatal B cells was significantly enhanced by co-cultures with memory, but not naive, CD4+ T cells. Memory CD4+ T cells were further divided into two populations based on expression of homing receptor L-selectin. These memory CD4+ T cell subpopulations appeared to behave in different fashions concerning help for Ig production by naive (sIgD+) and mature (sIgD-) B cells. L-selectin-negative memory CD4+ T cells exhibited helper function for Ig secretion by mature B cells. Intriguingly, Ig production by neonatal B cells as well as adult naive B cells, although less than that by mature B cells, was efficiently promoted by L-selectin-positive memory CD4+ T cells rather than L-selectin-negative ones. The results suggest that the capability of neonatal naive B cells to secrete IgG and IgA can be elicited by appropriate T-cell signals, especially from the L-selectin-positive population within memory CD4+ T cells, seemingly indicating its possible role for isotype switching in B cells.