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Mannose-Binding Lectin A-Deficient Mice Have Abrogated Antigen-Specific IgM Responses and Increased Susceptibility to a Nematode Infection¹

Tim Carter^*, Michiko Sumiya^*, Kerri Reilly^*, Rubina Ahmed, Peter Sobieszczuk^2,*, John A. Summerfield^* and Rachel A. Lawrence^3,

^* Department of Medicine, Imperial College London, St. Mary’s Campus, London; and Royal Veterinary College, Royal College Street, London, United Kingdom.

To investigate the role of mannose-binding lectin-A (MBL-A) in protection against infectious disease, MBL-A^–/–-deficient mice were generated. Using a well-characterized mouse model of human filarial nematode infection, nematode survival and protective immune responses were tested in vivo. Blood-borne Brugia malayi microfilariae survived for significantly longer time periods in MBL-A^–/– than in wild-type (WT) mice. However, no differences in either splenic cytokine responses or induction of leukocytes in the blood were observed. A profound abrogation of Ag-specific IgM levels was measured in B. malayi-infected MBL-A^–/– mice, and some IgG isotypes were higher than those observed in WT animals. To establish whether there was a defect in Ab responses per se in MBL-A^–/– mice or the effect was specific to filarial infection, we immunized these mice with OVA or a carbohydrate-free protein. Significantly, Ag-specific IgM responses were defective to both of these Ags, and Ag-specific IgG responses were largely unaffected. Furthermore, in naive mice, total IgM levels did not differ between MBL-A^–/– and WT mice. This article describes the first demonstration that MBL-A may function independently of MBL-C and suggests that MBL-A, like other C-type lectins and members of the complement cascade, is intimately involved in the priming of the humoral Ab response.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Wellcome Trust.

² Current address: The Scripps Research Institute, Consortium for Functional Glycomics, Mouse TransGenics, 10550 North Torrey Pines Road, Mail SP-145 La Jolla, CA 92037.

³ Address correspondence and reprint requests to Dr. Rachel Lawrence, Royal Veterinary College, University of London, Department of Immunology, Royal College Street, London, NW1 OTU U.K. E-mail address: rlawrence{at}rvc.ac.uk

⁴ Abbreviations used in this paper: MBL, mannose-binding lectin; WT, wild type; Mf, microfilariae; MfAg, soluble Mf extract; p.i., postimmunization; GC, germinal center; Sn, sialoadhesin.

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