|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1997 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1996 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1995 : ¥900,000 (Direct Cost : ¥900,000)
B cell immunoglobulin production is regulated by direct interaction and cytokines of helper T cells. In the present studies, wer had functionally analyzed CD27 in cord and peripheral blood B cells. Adult peripheral blood B cells were separated into CD27+ and CD27- cells, which were different in the morphology. Cord blood B cells did not express CD27, and CD27 expression on peripheral blood B cells increased with age in parallel. Only CD27+ B cells had ability to produce immunoglobulin, which was increased by contact with a TNF-related transmembrane ligand, CD70. Adult peripheral blood CD27+ B cells can be further subdivided into two discrete subtypes : IgD-CD27+ and IgD+CD27+B cells. IgD-CD27+B cells produced IgG,IgM and IgA,where as IgD+CD27+B cells predominantly produce IgM.The addition of activated CD4+CD45ROT cells with CD70 caused down-regulation of CD27 expression on activated B cells, and its down modulation was completely blocked by anti-CD70 mAb, indicating direct T-B cell con
tact via CD27/CD70. The triggering via CD27 and CD40 additively increased the immunoglobulin production under SAC plus IL-2 stimulation.
The triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). The differentiation into plasma cells by a combination of IL-10 and CD70-transfectants occurred in CD27+B cells, but not in CD27-B cells. Moreover, the addition of IL-2 to the IL-10 and CD70-transfect activation system greatly induced the differentiation into plasma cells. In the presence of only IL-2, IL-4 or IL-6, CD70-transfectants did not promote the differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B cell pool from peripheral blood B cells primarily activated by IL-2, IL-10 and anti-CD40 mAb. Finally, CD27 signaling also rescued B cells from IL-10-mediated apoptosis. Taken together, our findings demonstrate peripheral blood B cells are separated into subpopulations by CD27 and IgD expression and that CD27+B cells produce large amounts of immunoglobulin by the interaction with CD70 molecule. These data also demonstrate that CD27 ligand (CD70) is a key molecule to prevent the IL-10-mediated promotion of apoptosis and to direct the differentiation of CD27+memory B cells toward plasma cells in cooperation with IL-10.