title: B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.
abstract: We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.
authors.affiliation: Department of Inflammation, Wyeth Research, Cambridge, MA, USA. kdunussi@wyeth.com
authors.forename: Kyri
authors.initials: K
authors.lastname: Dunussi-Joannopoulos
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Hancock
authors.forename: Arthur
authors.initials: A
authors.lastname: Kunz
authors.forename: Martin
authors.initials: M
authors.lastname: Hegen
authors.forename: Xiaochuan X
authors.initials: XX
authors.lastname: Zhou
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Sheppard
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lamothe
authors.forename: Evelyn
authors.initials: E
authors.lastname: Li
authors.forename: Hak-Ling
authors.initials: HL
authors.lastname: Ma
authors.forename: Philip R
authors.initials: PR
authors.lastname: Hamann
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Damle
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000628:therapy*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D049109:Cell Proliferation; D024043:Collagen Type II / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000097:blood; D007156:Immunologic Memory; D007249:Inflammation; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism; D022261:Respiratory Syncytial Virus Vaccines; D012136:Respiratory Syncytial Viruses / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors
chemical_list: D024043:Collagen Type II; D007075:Immunoglobulin M; D022261:Respiratory Syncytial Virus Vaccines