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Journal of Virology, July 2006, p. 7111-7117, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.01421-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Optimal Long-Term Humoral Responses to Replication-Defective Herpes Simplex Virus Require CD21/CD35 Complement Receptor Expression on Stromal Cells

Mark A. Brockman,1,3,{dagger} Admar Verschoor,2,4,{ddagger} Jia Zhu,1,§ Michael C. Carroll,2,4 and David M. Knipe1,3*

Departments of Microbiology and Molecular Genetics,1 Pediatrics and Pathology,2 Program in Virology, Harvard Medical School,3 CBR Institute for Biomedical Research, 200 Longwood Avenue, Boston, Massachusetts 021154

Received 8 July 2005/ Accepted 27 April 2006

Replication-defective herpes simplex virus (HSV) strains elicit durable immune responses and protect against virulent HSV challenge in mice, despite being unable to establish latent infection in neuronal cells. Mechanisms for generating long-lived immunity in the absence of viral persistence remain uncertain. In animals immunized with replication-defective HSV, durable serum immunoglobulin G (IgG) responses were elicited. Surprisingly, Western blot analyses revealed that the specificities of antiviral IgG changed over time, and antibody reactivity to some viral proteins was detected only very late. Thus, some of the durable IgG activity appeared to be contributed by either new or significantly enhanced antibody responses at late times. Following immunization, radiation bone marrow-chimeric mice lacking complement receptors CD21 and CD35 on stromal cells elicited only short-lived serum IgG and failed to mount recall responses to subsequent HSV exposure. Our results suggest that complement-mediated retention of viral antigens by stromal cells, such as follicular dendritic cells, is critical for optimal maintenance of antibody responses and B-cell memory following vaccination with replication-defective HSV.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115. Phone: (617) 432-1934. Fax: (617) 432-0223. E-mail: David_Knipe{at}hms.harvard.edu.

{dagger} Present address: Massachusetts General Hospital, Boston, MA 02129.

{ddagger} Present address: Institute of Experimental Immunology, Zurich, Switzerland.

§ Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109.

Journal of Virology, July 2006, p. 7111-7117, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.01421-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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