The Regulation of Polysaccharide Specific Humoral Immune Response Against Intact Streptococcus Pneumoniae
Abstract
The adaptive immune response against isolated polysaccharides (PS) is T cell-independent. In contrast, the IgG anti-capsular PS response to both intact Streptococcus pneumoniae (Pn), as well as a soluble covalent conjugate of Pn-derived protein and PS,require CD4+T cell help, B7-dependent costimulation, and CD40-CD40-ligandinteractions. However, the IgG anti-PS response elicited by intact Pn, in contrast to soluble conjugate, peaks more rapidly, entails a shorter period of T cell help, and fails to induce PS-specific memory. Thus, the same antigen present in different physical/biochemical contexts elicits distinctly different humoral responses. The mechanism underlying these differences remains unknown and has important implications for the design of effective anti-PS vaccines against extracellular bacteria. One potential reason for the limited anti-PS response to Pn is that PS-specific B cells exhibit greater levels of apoptosis in response to this form of immunogen. We therefore studied mice that constitutively expressed the antiapoptotic protein Bcl-xL orBcl-2 as a B cell-specific transgene. We show that apoptosis limits a primary PS-specific Ig response to Pn, but does not account for the lack of PS-specific memory. The humoral immune response to intact Pn versus soluble Pn-derived conjugate is elicited through distinct pathways. We were thus interested in determining whether these pathways were activated independently or were cross-regulatory. We show that when soluble conjugate is co-injected with Pn, the generation of PS-specific memory, as well as the primary and memory protein-specific response, to the conjugate is abrogated. The mechanism of inhibition is an early event and is neither capsular PS- or protein-specific, nor based on the particulate nature of the Pn. [truncated]
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 19, 2008
- Accession Number
- AD1013512
Entities
People
- Gouri Chattopadhyay
Organizations
- Uniformed Services University of the Health Sciences