title: Mouse CD20 expression and function.
abstract: 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 IgM(hi) 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 approximately 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 Ca(2+) 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.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Junji
authors.initials: J
authors.lastname: Uchida
authors.forename: Youngkyun
authors.initials: Y
authors.lastname: Lee
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Liang
authors.forename: Alice
authors.initials: A
authors.lastname: Bradney
authors.forename: Julie A
authors.initials: JA
authors.lastname: Oliver
authors.forename: Kristina
authors.initials: K
authors.lastname: Bowen
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Karen M
authors.initials: KM
authors.lastname: Haas
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Poe
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018951:Antigens, CD20 / Q000276:immunology* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D006825:Hybridomas; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D007075:Immunoglobulin M; D002118:Calcium