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Infection and Immunity, February 2006, p. 1419-1424, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1419-1424.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Induction of In Vivo Antipolysaccharide Immunoglobulin Responses to Intact Streptococcus pneumoniae Is More Heavily Dependent on Btk-Mediated B-Cell Receptor Signaling than Antiprotein Responses

Abdul Q. Khan,1 Goutam Sen,1 Shuling Guo,2 Owen N. Witte,2 and Clifford M. Snapper1*

Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814,1 Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, 675 Charles E. Young Dr. S., 5-748 MRL, Los Angeles, California 90095-16622

Received 18 August 2005/ Returned for modification 14 October 2005/ Accepted 23 November 2005

The relative role of Btk-dependent B-cell receptor (BCR) signaling in the induction of antipolysaccharide (anti-PS) and antiprotein immunoglobulin (Ig) responses to an intact extracellular bacterium in vivo is unknown. Btklow mice exhibit reduced BCR signaling but largely restore B-cell development. Btklow mice immunized with intact Streptococcus pneumoniae elicit reduced anti-PS but normal antiprotein Ig responses. Immunization of Btklow mice with PS-protein conjugate in saline results in an even more profound defect in the anti-PS but not antiprotein response, which is largely restored by use of a CpG-containing oligodeoxynucleotide as an adjuvant. These data demonstrate a greater dependence on Btk-mediated BCR signaling for physiologic anti-PS relative to antiprotein responses, as well as the existence of a compensatory Toll-like-receptor-mediated signaling pathway naturally triggered in response to intact bacterial pathogens.

* Corresponding author. Mailing address: Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799. Phone: (301) 295-3490. Fax: (301) 295-1640. E-mail: csnapper{at}usuhs.mil.

Editor: J. N. Weiser

Infection and Immunity, February 2006, p. 1419-1424, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1419-1424.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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