Direct B/B-cell interactions in immunoglobulin synthesis.

The principal roles of B/B-cell interactions in immune response have not yet been established. We therefore investigated B/B-cell interactions in immunoglobulin synthesis via direct cell-to-cell contact, particularly in the tumour necrosis factor receptor (TNFR)/tumour necrosis factor (TNF) family. We prepared highly purified peripheral blood B cells and stimulated them with Epstein--Barr virus (EBV)-transformed B lymphoblastoid cell lines (LCLs) as activated human B cells. The IgG production by B cells was increased by the addition of fixed LCLs in a dose-dependent manner in the presence of IL-10 plus IL-2. LCLs strongly expressed CD40 and CD70 on their surface, but marginal or no CD154, CD27, OX40 (CD134) and CD134 ligand. The enhancement of immunoglobulin production by LCLs was completely blocked by the initial addition of anti-CD70 blocking MoAb, but not by anti-CD154 or anti-CD134 ligand MoAb. The addition of LCLs also caused a reduction in CD27 expression on B cells, and this effect was completely blocked by anti-CD70 MoAb, indicating a direct B cell--LCL contact via CD27/CD70. LCLs markedly promoted B-cell differentiation into plasma cells in the presence of IL-10 plus IL-2. These findings demonstrate that direct interactions between B and B cells via CD27/CD70 induce immunoglobulin production by promoting the generation of plasma cells.