Optimal long-term humoral responses to replication-defective herpes simplex virus require CD21/CD35 complement receptor expression on stromal cells.
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.
Brockman
Mark A
MA
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Verschoor
Admar
A
Zhu
Jia
J
Carroll
Michael C
MC
Knipe
David M
DM
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016026:Bone Marrow Transplantation; D002522:Chlorocebus aethiops; D003165:Complement System Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D022301:Herpes Simplex Virus Vaccines / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009474:Neurons / Q000276:immunology / Q000821:virology; D017463:Receptors, Complement 3b / Q000235:genetics / Q000276:immunology*; D017464:Receptors, Complement 3d / Q000235:genetics / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology; D013997:Time Factors; D018183:Transplantation Chimera / Q000276:immunology; D014709:Vero Cells; D017735:Virus Latency / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics
D000914:Antibodies, Viral; D000956:Antigens, Viral; D022301:Herpes Simplex Virus Vaccines; D007074:Immunoglobulin G; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D003165:Complement System Proteins