Differential regulation of IgG anti-capsular polysaccharide and antiprotein responses to intact Streptococcus pneumoniae in the presence of cognate CD4+ T cell help

J Immunol. 2004 Jan 1;172(1):532-9. doi: 10.4049/jimmunol.172.1.532.

Abstract

The relative lack of memory for IgG antipolysaccharide responses is believed to be secondary to the inability of polysaccharides to associate with MHC class II molecules and thus a failure to recruit cognate CD4+ T cell help. However, little is known concerning the role of T cells and the generation of memory for antipolysaccharide Ig responses to intact extracellular bacteria. We used heat-killed, intact Streptococcus pneumoniae, capsular type 14 (Pn14), to evaluate the IgM and IgG responses specific for the capsular polysaccharide (PPS14), the phosphorylcholine determinant of the cell wall C-polysaccharide, and the cell wall protein, pneumococcal surface protein A (PspA). We demonstrate that the IgG (but not IgM), anti-PPS14, and anti-PspA responses to Pn14 are CD4+ T cell dependent and TCR specific. Nevertheless, in contrast to the anti-PspA response, the IgG anti-PPS14 response shows no apparent memory, an accelerated kinetics of primary Ig induction, and a more rapid delivery of CD4+ T cell help. In contrast, the IgG anti-phosphorylcholine response, although also dependent on CD4+ T cells, is TCR nonspecific. We make similar observations using soluble conjugates of PPS14-PspA and C-polysaccharide-PspA. These data lead us to suggest that the central issue concerning the mechanisms underlying different functional outcomes for anti-bacterial IgG responses to capsular polysaccharide vs protein Ags is not necessarily based on the ability to recruit cognate CD4+ T cell help, but perhaps on the nature of the B cell Ag receptor signaling that occurs and/or on the responding B cell subpopulations.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis*
  • Bacterial Capsules / administration & dosage
  • Bacterial Capsules / immunology*
  • Bacterial Proteins / administration & dosage
  • Bacterial Proteins / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / microbiology*
  • CD40 Ligand / physiology
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Immunization, Secondary
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin M / biosynthesis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Mice, Transgenic
  • O Antigens / administration & dosage
  • O Antigens / immunology
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / immunology
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / immunology*
  • Pneumococcal Vaccines / pharmacokinetics
  • Receptors, Antigen, T-Cell / deficiency
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Solubility
  • Streptococcus pneumoniae / immunology*
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / immunology
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • Epitopes, T-Lymphocyte
  • Immunoglobulin G
  • Immunoglobulin M
  • O Antigens
  • Pneumococcal Vaccines
  • Receptors, Antigen, T-Cell
  • Vaccines, Conjugate
  • Vaccines, Inactivated
  • pneumococcal polysaccharide, type 14
  • pneumococcal surface protein A
  • Phosphorylcholine
  • CD40 Ligand