title: Effective collaboration between IL-4 and IL-21 on B cell activation.
abstract: Although IL-4 and IL-21 synergistically promote proliferation and differentiation of activated B cells, the mutual role in their collaboration is not known. When splenic B cells were sequentially stimulated with anti-IgM Ab and anti-CD40 Ab plus IL-4 and then with IL-21 at a 2-day interval, proliferation, frequency of class switching to IgG1 and plasma cell differentiation were continuously enhanced until day 5 of culture. Amounts of AID and Blimp1 mRNA in sequentially activated B cells with IL-4 and IL-21 increased more than those in activated B cells without IL-21. However, sequential stimulation of B cells with anti-IgM Ab and anti-CD40 Ab plus IL-21 and then with IL-4 at more than 1-day interval did not display the synergistic effect. Furthermore, sequential stimulation of activated B cells with a low dose of IL-4, which did not induce Ig class switching, at the beginning of culture and with IL-21 or IL-4 on day 2 of culture induced proliferation and differentiation of CXCR4(-) or CXCR4(+) B cells, respectively. Thus, IL-21 effectively promotes proliferation and differentiation of CXCR4(-) B cells pre-activated with anti-IgM Ab and anti-CD40 Ab plus IL-4.
authors.affiliation: Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Saito
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitayama
authors.forename: Akemi
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Tsuruoka
authors.forename: Masafumi
authors.initials: M
authors.lastname: Arima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D007075:Immunoglobulin M / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D000098546:Interleukin-21
chemical_list: D000906:Antibodies; D019013:CD40 Antigens; D007075:Immunoglobulin M; D007378:Interleukins; D015847:Interleukin-4; D000098546:Interleukin-21