| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This project was supported by National Institutes of Health Grants CA96547, CA105001, and AI056363. K.M.H. was supported by a Special Fellow Award from the Leukemia and Lymphoma Society and by a Small Project Grant from the Duke Center for Translational Research.
2 Address correspondence and reprint requests to Dr. Thomas F. Tedder, Department of Immunology, Box 3010, Duke University Medical Center, Durham, NC 27710. E-mail address: thomas.tedder{at}duke.edu
3 Abbreviations used in this paper: TI, T cell independent; [Ca2+]i, intracellular calcium; CHO, Chinese hamster ovary; KLH, keyhole limpet hemocyanin; MZ, marginal zone; PD-1, programmed cell death 1; PPS, pneumococcal polysaccharide; rBlyS, recombinant B lymphocyte stimulator; TD, T cell dependent; Tg, transgenic; TNP, trinitrophenyl.
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
