title: Restoration of T cell-independent type 2 induction of Ig secretion by neonatal B cells in vitro.
abstract: The humoral immune response of neonates to T cell-independent type 2 (TI-2) Ags is markedly defective. We previously demonstrated that multivalent 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 other modes of B cell activation, relative to adult B cells. However, costimulation of anti-Ig-dextran-activated neonatal B cells with either CD40-ligand, a recombinant bacterial lipoprotein, or LPS restores the IgM 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 response to TI-2 Ags if adequate costimuli are provided, and thus may have particular relevance for the design of vaccine strategies in the immunodeficient host. The data also suggest that neonatal B cells are programmed to secrete relatively enhanced amounts of IgE and IgA, which may be relevant for antimicrobial resistance at mucosal surfaces.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Snapper
authors.forename: F R
authors.initials: FR
authors.lastname: Rosas
authors.forename: M A
authors.initials: MA
authors.lastname: Moorman
authors.forename: J J
authors.initials: JJ
authors.lastname: Mond
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000276:immunology*; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000954:Antigens, Surface / Q000494:pharmacology; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology; D001428:Bacterial Vaccines; D019013:CD40 Antigens / Q000494:pharmacology; D023201:CD40 Ligand; D003911:Dextrans / Q000494:pharmacology; D004338:Drug Combinations; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000276:immunology; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000954:Antigens, Surface; D000955:Antigens, T-Independent; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D019013:CD40 Antigens; D003911:Dextrans; D004338:Drug Combinations; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D007136:Immunoglobulins; D008024:Ligands; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; C072045:OspA protein; D023201:CD40 Ligand; D007073:Immunoglobulin E