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Cutting Edge: Primary and Secondary Effects of CD19 Deficiency on Cells of the Marginal Zone¹

Yuying You^*, Hong Zhao, Yue Wang^2, and Robert H. Carter^3,

^* Department of Microbiology and Department of Medicine, University of Alabama at Birmingham, Birmingham AL 35294; and National Institute of Arthritis, Musculoskeletal and Skin Disease, Bethesda, MD 20892

Marginal zone (MZ) B cells are absent in CD19^–/– mice. Possible causes include an intrinsic defect in B cells and/or a secondary defect in the extrinsic MZ microenvironment as a result of changes in B cell differentiation in mice lacking CD19. Cells in the MZ also include MZ macrophages (MZM) and MZ dendritic cells (DC). Although CD19 is only expressed on B cells, SIGN-R1⁺ MZM are absent and CD11c⁺ MZ DC distribution is abnormal in CD19^–/– mice. Adoptively transferred B cells from normal mice are able to reconstitute MZ B cells in CD19^–/– mice. In contrast, CD19^–/– B cells could not enter the MZ of the normal mice. Furthermore, MZM distribution and MZ DC distribution are restored following MZ B cell reconstitution in CD19^–/– mice. Thus, MZ B cells are required for MZM differentiation and MZ DC localization, but the deficiency of MZ B cells in CD19^–/– mice is caused by a defect of intrinsic B cell signaling.

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 National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health Grant RO1 AI 46225 (to R.H.C.) and the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (to R.H.C.).

² Current address: MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878.

³ Address correspondence and reprint requests to Dr. Robert H. Carter, Building 31, Room 4C32, 31 Center Drive, Mail Stop Code 2350, Bethesda, MD 20892-2350. E-mail address: carterrob{at}mail.nih.gov

⁴ Abbreviations used in this paper: FO, follicular; CD19ko, CD19 knockout; DC, dendritic cell; MMM, marginal metallophilic macrophage; MZ, marginal zone; MZM, marginal zone macrophage; WT, wild type.

⁵ The online version of this article contains supplemental material.