Human CD22 cannot fully substitute murine CD22 functions in vivo, as shown in a new knockin mouse model

Wöhner M, Born S, Nitschke L (2012)


Publication Status: Published

Publication Type: Journal article

Publication year: 2012

Journal

Publisher: WILEY-BLACKWELL

Book Volume: 42

Pages Range: 3009-3018

Journal Issue: 11

DOI: 10.1002/eji.201242629

Abstract

CD22, an inhibitory co-receptor of the B-cell receptor, shows a B-cell-specific expression pattern and is expressed on most B-cell lymphomas. The anti-CD22 antibody Epratuzumab is in clinical trials for B-cell non-Hodgkin lymphoma and systemic lupus erythematosus, but shows a mostly unknown mode of action. We generated a new mouse model that expresses human CD22 instead of murine CD22 (Huki CD22 mice), in which human CD22 can be targeted. Expression of human CD22 on the B cells of Huki CD22 mice does not generally interfere with B-cell development. However, Huki CD22 mice show a reduction of the population of mature recirculating B cells in the bone marrow and reduced transitional and marginal zone B cells in the spleen, phenotypes resembling that of CD22-deficient mice. Similarly, enhanced BCR-induced Ca2+ signalling is observed in Huki CD22 mice, which also mount normal immune responses toward different classes of antigens. Huki CD22 B cells show a normal anti-hCD22 antibody-mediated endocytosis. In conclusion, human CD22 cannot fully substitute for murine CD22 functions, possibly due to the changed intracellular tail of the protein or due to lower expression levels. Huki CD22 mice are a valuable new model for both antibody- and immunotoxin-mediated targeting of human CD22.

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How to cite

APA:

Wöhner, M., Born, S., & Nitschke, L. (2012). Human CD22 cannot fully substitute murine CD22 functions in vivo, as shown in a new knockin mouse model. European Journal of Immunology, 42(11), 3009-3018. https://doi.org/10.1002/eji.201242629

MLA:

Wöhner, Miriam, Stefanie Born, and Lars Nitschke. "Human CD22 cannot fully substitute murine CD22 functions in vivo, as shown in a new knockin mouse model." European Journal of Immunology 42.11 (2012): 3009-3018.

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