Journal
IMMUNOBIOLOGY
Volume 213, Issue 7, Pages 545-555Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.imbio.2008.01.006
Keywords
B lymphocytes; cellular differentiation; Ig class switching; cytokines
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Funding
- Ministry of Education, Science, Technology, Sports and Culture of Japan
- Uehara Memorial Foundation
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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. (C) 2008 Elsevier GmbH. All rights reserved.
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