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

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


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Disease Models, Animal
  • Humans
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Transgenic
  • Peanut Hypersensitivity / genetics
  • Peanut Hypersensitivity / immunology*
  • Peanut Hypersensitivity / pathology
  • Peyer's Patches / immunology*
  • Peyer's Patches / pathology
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology*
  • Sialic Acid Binding Ig-like Lectin 2 / genetics
  • Sialic Acid Binding Ig-like Lectin 2 / immunology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*


  • CD22 protein, human
  • Cd22 protein, mouse
  • Receptors, Antigen, B-Cell
  • Sialic Acid Binding Ig-like Lectin 2