Limited Expression of APRIL and its Receptors Prior to Intestinal IgA Plasma Cell Development During Human Infancy

The absence of immunoglobulin A (IgA) in the intestinal tract renders young infants highly susceptible to enteric infections. However, mediators of initial IgA induction in this population are undefined. We determined the temporal acquisition of plasma cells by isotype and expression of T cell-independent (TI) and -dependent (TD) IgA class switch factors in the human intestinal tract during early infancy. We found that IgA plasma cells were largely absent in the infant intestine until after one month of age, approaching adult densities later in infancy than both IgM and IgG. The restricted development of IgA plasma cells in the first month was accompanied by reduced expression of the TI factor APRIL and its receptors TACI and BCMA within isolated lymphoid follicles (ILFs). Moreover, APRIL and BCMA expression both strongly correlated with increasing IgA plasma cell densities over time. Conversely, TD mediators (CD40L and CD40) were expressed within ILFs prior to one month and were not associated with IgA plasma cell generation. In addition, preterm infants had lower densities of IgA plasma cells and reduced APRIL expression compared with full term infants. Thus, blunted TI responses may contribute to the delayed induction of intestinal IgA during early human infancy.