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Complement Receptors 1 and 2 Influence the Immune Environment in a B Cell Receptor-Independent Manner^1,2

Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132

The CD21/35 proteins are complement receptors implicated in controlling and interpreting activation states of the innate and acquired immune responses. One defect of CD21/35^–/– animals is depressed production of Ag-specific IgG3 which we show is evident in vivo but not in vitro. Gene expression profiles obtained from naive wild-type and CD21/35^–/– splenocytes demonstrated enhanced expression of inflammatory mediators from CD11b⁺ splenocytes in the CD21/35^–/– animals. Splenocyte populations between wild-type and CD21/35^–/– mice were similar except for a moderate increase in GR1^lowCD31⁺ immature myeloid cells. Furthermore, depletion of neutrophils and other GR1-expressing cells alleviates elevated inflammatory gene expression in the CD21/35^–/– spleen. Complement activation also plays a key role in the differential gene expression observed in the CD21/35-deficient mouse as depletion of C3 or inhibition of C3a receptor signaling within the animal returned inflammatory gene expression within the spleen to wild-type levels. Finally, C3 depletion before immunization allowed for the enhanced production of Ag-specific IgG3 production in the CD21/35^–/– mouse compared with mock-depleted animals. These data suggest that the overall environment of the CD21/35^–/– spleen is quite different from that of the wild-type animal perhaps due to altered complement convertase activity. This difference may be responsible for a number of the phenotypes ascribed to the deficiency of CD21/35 proteins on B cells and follicular dendritic cells.

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¹ This work was supported by National Institute of Allergy and Infectious Diseases Grants AI-24158 (to J.H.W.) and AI-32223 (to J.J.W.). A.C.J. was supported by Training Program in Microbial Pathogenesis 5T32-AI-055434.

² The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

³ Address correspondence and reprint requests to Dr. John H. Weis, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, Salt Lake City, UT 84112. E-mail address: john.weis{at}path.utah.edu

⁴ Abbreviations used in this paper: CR1, complement receptor 1; CR2, complement receptor 2; CR3, complement receptor 3; CR4, complement receptor 4; FDC, follicular dendritic cell; CVF, cobra venom factor; I-C3, I-C3 germline transcript; C3aRA, C3a receptor antagonist; WT, wild type; TNP, trinitrophenol.

⁵ The online version of this article contains supplemental material.

This article has been cited by other articles:

				A. C. Jacobson and J. H. Weis Comparative Functional Evolution of Human and Mouse CR1 and CR2 J. Immunol., September 1, 2008; 181(5): 2953 - 2959. [Full Text] [PDF]