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International Immunology, Vol. 16, No. 1, pp. 119-129, January 2004
© 2004 Japanese Society for Immunology

Mouse CD20 expression and function

Junji Uchida1, Youngkyun Lee1, Minoru Hasegawa1, Yinghua Liang1, Alice Bradney1, Julie A. Oliver1, Kristina Bowen1, Douglas A. Steeber1, Karen M. Haas1, Jonathan C. Poe1 and Thomas F. Tedder1

1 Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA

Correspondence to: T. F. Tedder; E-mail thomas.tedder{at}duke.edu
Transmitting editor: S. Koyasu

CD20 plays a role in human B cell proliferation and is an effective target for immunotherapy. In this study, mouse CD20 expression and biochemistry were assessed for the first time using a new panel of CD20-specific mAb, with CD20 function assessed using CD20-deficient (CD20–/–) mice. CD20 expression was B cell restricted and was initiated during late pre-B cell development. The frequency and density of CD20 expression increased during B cell maturation in the bone marrow, with a subpopulation of transitional IgMhi B cells expressing higher CD20 levels than the majority of mature recirculating B cells. Transitional T1 B cells in the spleen also expressed high CD20 levels, providing a useful new marker for this B cell subset. In CD20–/– mice, immature and mature B cell IgM expression was ~20–30% lower relative to B cells from wild-type littermates. In addition, CD19-induced intracellular calcium responses were significantly reduced in CD20–/– B cells, with a less dramatic effect on IgM-induced responses. These results reveal a role for CD20 in transmembrane Ca2+ movement in mouse primary B cells that complements previous results obtained using human CD20 cDNA-transfected cell lines. Otherwise, B cell development, tissue localization, signal transduction, proliferation, T cell-dependent antibody responses and affinity maturation were normal in CD20–/– mice. Thus, mouse and human CD20 share similar patterns of expression and function. These studies thereby provide an animal model for studying CD20 function in vivo and the molecular mechanisms that influence anti-CD20 immunotherapy.

Keywords: B lymphocyte, immunotherapy, knockout mouse, mAb, signal transduction


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