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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2235-2243.
Prepublished online as a Blood First Edition Paper on June 9, 2005; DOI 10.1182/blood-2004-11-4547.
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Submitted December 1, 2004
Accepted May 23, 2005
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
Kyri Dunussi-Joannopoulos*, Gerald E Hancock, Arthur Kunz, Martin Hegen, Xiaochuan X Zhou, Barbara J Sheppard, Jennifer Lamothe, Evelyn Li, Hak-Ling Ma, Philip R Hamann, Nitin K Damle, and Mary Collins
Department of Inflammation, Wyeth Research, Cambridge, MA, USA
Department of Wyeth Vaccines, Wyeth Research, Cambridge, MA, USA
Department of Chemical & Screening Sciences, Wyeth Research, Cambridge, MA, USA
Department of Investigative Pathology, Wyeth Research, Cambridge, MA, USA
Department of Oncology Discovery, Wyeth Research, Cambridge, MA, USA
* Corresponding author; email: kdunussi{at}wyeth.com.
We report the development of a mouse B cell depleting immunoconjugate (anti-CD22 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; (i) the immunoconjugate has B cell specific in-vitro and in-vivo cytotoxicity; (ii) B cell reconstitution starts in bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (iii) B cell depletion inhibits the development of clinical and histological arthritis in the CIA model; (iv) depletion of type-II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; (v) 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.
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