title: Immunization with autologous CD46 generates a strong autoantibody response in rats that targets spermatozoa.
abstract: CD46, a membrane complement regulator, has been implicated as pathogen receptor, T cell activator and contributor to spermatozoa-egg interactions. In man, a role in the fertilization process was suggested by its localization on the acrosome. In rodents, CD46 is expressed only on the spermatozoal acrosome, suggesting an essential role at this site. This restricted expression led us to ask whether immunization with CD46 would generate anti-CD46 antibody responses that might target spermatozoa and influence fertility. We immunized male and female rats with rat CD46. Strong immune responses were generated in all rats and immune sera stained CD46 in testis extracts and in situ in testis and sperm. Incubation of spermatozoa with immune sera caused deposition of immunoglobulin and C3b in an acrosome pattern and reduced motility. We mated immune male rats with naïve females and female immune rats with naïve males. The incidence of pregnancy and number of fetuses were not different in matings involving immune male or female rats compared to controls. Testis sections from immune rats revealed no immunoglobulin deposition on CD46-positive sperm precursors, suggesting that acrosomal CD46 was inaccessible in this location. A minority of spermatozoa harvested from epididymis of immune rats had immunoglobulin and C3b bound to the acrosome, suggesting that anti-CD46, present in genital tract fluids, bound after acrosome reaction. These data demonstrate that the restricted expression of CD46 allows strong anti-CD46 responses in rats that target spermatozoa in vitro and in vivo. The anti-CD46 response did not influence fertility, perhaps reflecting the considerable redundancy for fertilization in rodents.
authors.affiliation: Complement Biology Group, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Complement Biology Group, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Harris
authors.affiliation: Complement Biology Group, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, UK. Electronic address: morganbp@cardiff.ac.uk.
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
mesh_terms: D000177:Acrosome / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology; D005260:Female; D007114:Immunization; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051916:Membrane Cofactor Protein / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013081:Sperm Motility / Q000187:drug effects / Q000276:immunology*; D013084:Sperm-Ovum Interactions / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; C497860:Cd46 protein, rat; D051916:Membrane Cofactor Protein; D003179:Complement C3b