RESTORATION OF T-CELL-INDEPENDENT TYPE-2 INDUCTION OF IG SECRETION BYNEONATAL B-CELLS IN-VITRO

The humoral immune response of neonates to T cell-independent type 2 ( TI-2) Ags is markedly defective. We previously demonstrated that multi valent membrane Ig cross-linking, using dextran-conjugated anti-Ig Abs (anti-Ig-dextran), is an in vitro model for membrane Ig-dependent TI- 2 induction of Ig secretion. In this work, we demonstrate that highly purified neonatal B cells are intrinsically defective in IgM secretion in response to anti-Ig-dextran and cytokines in vitro, as well as oth er modes of B cell activation, relative to adult B cells. However, cos timulation of anti-Ig-dextran-activated neonatal B cells with either C D40-ligand, a recombinant bacterial lipoprotein, or LPS restores the I gM secretory response of neonatal B cells to adult levels. Analysis of Ig isotype secretion indicates that neonatal B cells have an enhanced capacity to secrete IgE and IgA relative to other Ig isotypes. These data suggest that neonatal B cells are competent to secrete Ig in resp onse to TI-2 Ags if adequate costimuli are provided, and thus may have particular relevance for the design of vaccine strategies in the immu nodeficient host. The data also suggest that neonatal B cells are prog rammed to secrete relatively enhanced amounts of IgE and IgA, which ma y be relevant for antimicrobial resistance at mucosal surfaces.