Pioli C, Gatta L, Ubaldi V, Doria G
Section of Toxicology and Biomedicine, Ente per le Nuove Tecnologie, l'Energia et l'Ambiente C.R. Casaccia., Rome, Italy.
J Immunol. 2000 Nov 15;165(10):5530-6. doi: 10.4049/jimmunol.165.10.5530.
Although a large amount of information is available on the activity of CTLA-4 in T cells, the role of this receptor in B cells has not been previously characterized. Our results show that CD40 or LPS stimulation in the presence of IL-4 induces CTLA-4 expression in purified B cells; the maximum level is reached in both membrane and intracellular compartments after 48-72 h. Engagement of the B cell CTLA-4 by immobilized mAb inhibits IgG1 and IgE production and reduces the frequency of IgG1- and IgE-expressing B cells. Cepsilon and Cgamma(1) germline mRNA expression as well as NF-kappaB and STAT6 activation, events required for isotype switching, are also inhibited by CTLA-4 engagement. Together these findings show the critical role of CTLA-4 in the control of IL-4-driven isotype switching and suggest new approaches for modulating immediate-type hypersensitivity responses.
