CD21/35 promotes protective immunity to Streptococcus pneumoniae through a complement-independent but CD19-dependent pathway that regulates PD-1 expression.

Published

Journal Article

Humoral immunity to T cell-independent type 2 Ags (TI-2 Ag) is critical for protection against encapsulated bacteria such as Streptococcus pneumoniae. The CD21/35 receptor is thought to promote protective humoral immunity to encapsulated bacteria by enabling complement-decorated capsular polysaccharides to coligate the CD21/35-CD19 signaling complex with the B cell Ag receptor (BCR), thereby enhancing Ag-specific B cell activation. However, Ab responses to S. pneumoniae type 3 capsular polysaccharide (PPS-3) and other strong TI-2 Ags were significantly impaired in CD21/35(-/-) but not C3(-/-) or C4(-/-) mice. B cells from CD21/35(-/-) mice expressed significantly higher levels of cell surface CD19. CD21/35(-/-) B cells exhibited enhanced BCR-induced calcium responses and significantly higher expression of the inhibitory programmed death-1 (PD-1) receptor following immunization with a TI-2 Ag or BCR crosslinking. Reducing CD19 expression in CD21/35(-/-) mice normalized BCR-induced calcium responses, PD-1 induction, and PPS-3-specific IgG3 responses and restored protection during S. pneumoniae infection. PD-1 blockade also selectively rescued PPS-3-specific IgG3 responses in CD21/35(-/-) mice. Thereby, CD21/35 promotes protective humoral immunity to S. pneumoniae and other strong TI-2 Ags through a complement-independent pathway by negatively regulating CD19 expression and PD-1 induction.

Full Text

Duke Authors

Cited Authors

  • Haas, KM; Poe, JC; Tedder, TF

Published Date

  • September 15, 2009

Published In

Volume / Issue

  • 183 / 6

Start / End Page

  • 3661 - 3671

PubMed ID

  • 19710450

Pubmed Central ID

  • 19710450

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.0901218

Language

  • eng

Conference Location

  • United States