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J. Biol. Chem., Vol. 279, Issue 52, 54117-54123, December 24, 2004

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CD200 Receptor Family Members Represent Novel DAP12-associated Activating Receptors on Basophils and Mast Cells^*

David Voehringer, David B. Rosen¶||, Lewis L. Lanier||**, and Richard M. Locksley**

From the Departments of Medicine and ^¶Microbiology and Immunology, the ^**Cancer Research Institute, and Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California 94143-0654

Modulation by balancing activating and inhibitory receptors constitutes an important mechanism for regulating lymphocyte and myeloid cell effector responses. Using a microarray screen during parasitic helminth infection, we identified CD200 receptor-like 3 as a transcript highly expressed in basophils. Novel splice variants were present that generated proteins that differed in surface expression. The second immunoglobulin-like domain, encoded by exon 4, was required for cell surface expression and recruitment of DAP12 to the cell surface. Splice variants also generated unique cytoplasmic domains, which contributed to efficient pairing with DAP12. Despite expression on basophils and mast cells, which are integral components of allergic immunity, the absence of DAP12 did not alter effector cell recruitment or the host response elicited by helminth infection with Nippostrongylus brasiliensis.

Received for publication, June 23, 2004 , and in revised form, September 17, 2004.

^* This work was supported in part by NIAID Grant RO1 30663 and NHLBI Grant HL56385 from the National Institutes of Health. 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.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY703837–AY703842.

^|| Supported by National Institutes of Health Grant CA89294.

American Cancer Society Research Professor.

Senior Scholar of the Ellison Medical Foundation for Global Infectious Disease. To whom correspondence should be addressed: UCSF, Box 0654, C-443, 521 Parnassus Ave., San Francisco, CA 94143-0654. Tel.: 415-476-5859; Fax: 415-476-9364; E-mail: locksley{at}medicine.ucsf.edu.

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