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J Immunol. 2017 Nov 1;199(9):3116-3128. doi: 10.4049/jimmunol.1700898. Epub 2017 Sep 29.

Human CD22 Inhibits Murine B Cell Receptor Activation in a Human CD22 Transgenic Mouse Model.

Author information

1
Immunology Team, Janssen Research and Development, LLC, Raritan, NJ 08869.
2
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037.
3
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
4
Palo Alto Veterans Institute for Research, Palo Alto, CA 94304.
5
The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304.
6
Department of Immunology and Microbial Sciences, The Scripps Research Institute; La Jolla, CA 92037; and.
7
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
8
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037; macauley@ualberta.ca jpaulson@scripps.edu.

Abstract

CD22, a sialic acid-binding Ig-type lectin (Siglec) family member, is an inhibitory coreceptor of the BCR with established roles in health and disease. The restricted expression pattern of CD22 on B cells and most B cell lymphomas has made CD22 a therapeutic target for B cell-mediated diseases. Models to better understand how in vivo targeting of CD22 translates to human disease are needed. In this article, we report the development of a transgenic mouse expressing human CD22 (hCD22) in B cells and assess its ability to functionally substitute for murine CD22 (mCD22) for regulation of BCR signaling, Ab responses, homing, and tolerance. Expression of hCD22 on transgenic murine B cells is comparable to expression on human primary B cells, and it colocalizes with mCD22 on the cell surface. Murine B cells expressing only hCD22 have identical calcium (Ca2+) flux responses to anti-IgM as mCD22-expressing wild-type B cells. Furthermore, hCD22 transgenic mice on an mCD22-/- background have restored levels of marginal zone B cells and Ab responses compared with deficiencies observed in CD22-/- mice. Consistent with these observations, hCD22 transgenic mice develop normal humoral responses in a peanut allergy oral sensitization model. Homing of B cells to Peyer's patches was partially rescued by expression of hCD22 compared with CD22-/- B cells, although not to wild-type levels. Notably, Siglec-engaging antigenic liposomes formulated with an hCD22 ligand were shown to prevent B cell activation, increase cell death, and induce tolerance in vivo. This hCD22 transgenic mouse will be a valuable model for investigating the function of hCD22 and preclinical studies targeting hCD22.

PMID:
28972089
PMCID:
PMC5679471
DOI:
10.4049/jimmunol.1700898
[Indexed for MEDLINE]
Free PMC Article

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