CD27-CD70 Interactions Regulate B-Cell Activation by T Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-11, Vol.92 (24), p.11249-11253
• Main Authors: Kobata, Tetsuji, Jacquot, Serge, Kozlowski, Stacy, Agematsu, Kazunaga, Schlossman, Stuart F., Morimoto, Chikao
• Format: Article
• Language: English
• Subjects: Antigens, CD; B lymphocytes; B-Lymphocytes - physiology; CD27 Ligand; Cells, Cultured; Complementary DNA; Cultured cells; Humans; Immunoglobulin G - biosynthesis; Immunology; Ligands; Lymphocyte Activation; Lymphocyte Cooperation; Membrane Proteins - physiology; Monoclonal antibodies; Pretreatment; Secretion; T lymphocytes; T-Lymphocytes - physiology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - physiology; Tumor necrosis factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.24.11249

CD27, a member of the tumor necrosis factor (TNF) receptor family, binds to its ligand CD70, a member of the TNF family, and subsequently induces T-cell costimulation and B-cell activation. CD27 is expressed on resting T and B cells, whereas CD70 is expressed on activated T and B cells. Utilizing transfected murine pre-B-cell lines expressing human CD27 or CD70, we have examined the effect of such transfectant cells on human B-cell IgG production and B-cell proliferation. We show that the addition of CD27-transfected cells to a T-cell-dependent, pokeweed mitogen-driven B-cell IgG synthesis system resulted in marked inhibition of IgG production, whereas the addition of CD70-transfected cells enhanced IgG production. The inhibition and enhancement of pokeweed mitogen-driven IgG production by CD27 and CD70 transfectants were abrogated by pretreatment with anti-CD27 and anti-CD70 monoclonal antibodies, respectively. In contrast, little or no inhibition of IgG production and B-cell proliferation was noted with CD27-transfected cells or either anti-CD27 or CD70 monoclonal antibody in a T-cell-independent, Staphylococcus aureus/interleukin 2-driven B-cell activation system. In this same system CD70-transfected cells enhanced B-cell IgG production and B-cell proliferation, and this enhancement could be gradually abrogated by addition of increasing numbers of CD27-transfected cells. These results clearly demonstrate that interactions among subsets of T cells expressing CD27 and CD70 play a key role in regulating B-cell activation and immunoglobulin synthesis.