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,
Departments of
*
Pathology and
Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; and
Biosynexus, Gaithersburg, MD 20877
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.
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G. Chattopadhyay, A. Q. Khan, G. Sen, J. Colino, W. duBois, A. Rubtsov, R. M. Torres, M. Potter, and C. M. Snapper Transgenic Expression of Bcl-xL or Bcl-2 by Murine B Cells Enhances the In Vivo Antipolysaccharide, but Not Antiprotein, Response to Intact Streptococcus pneumoniae J. Immunol., December 1, 2007; 179(11): 7523 - 7534. [Abstract] [Full Text] [PDF]
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Q. Chen, G. Sen, and C. M. Snapper Endogenous IL-1R1 Signaling Is Critical for Cognate CD4+ T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to Intact Streptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine J. Immunol., November 1, 2006; 177(9): 6044 - 6051. [Abstract] [Full Text] [PDF]
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G. Sen, Q. Chen, and C. M. Snapper Immunization of Aged Mice with a Pneumococcal Conjugate Vaccine Combined with an Unmethylated CpG-Containing Oligodeoxynucleotide Restores Defective Immunoglobulin G Antipolysaccharide Responses and Specific CD4+-T-Cell Priming to Young Adult Levels Infect. Immun., April 1, 2006; 74(4): 2177 - 2186. [Abstract] [Full Text] [PDF]
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A. Jeurissen, A. D. Billiau, L. Moens, L. Shengqiao, W. Landuyt, G. Wuyts, L. Boon, M. Waer, J. L. Ceuppens, and X. Bossuyt CD4+ T Lymphocytes Expressing CD40 Ligand Help the IgM Antibody Response to Soluble Pneumococcal Polysaccharides via an Intermediate Cell Type J. Immunol., January 1, 2006; 176(1): 529 - 536. [Abstract] [Full Text] [PDF]
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K. S. Lee, G. Sen, and C. M. Snapper Endogenous CD4+ CD25+ Regulatory T Cells Play No Apparent Role in the Acute Humoral Response to Intact Streptococcus pneumoniae Infect. Immun., July 1, 2005; 73(7): 4427 - 4431. [Abstract] [Full Text] [PDF]
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