| First Author | Arens R | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 6 | Pages | 3901-8 |
| PubMed ID | 15356138 | Mgi Jnum | J:92744 |
| Mgi Id | MGI:3054463 | Doi | 10.4049/jimmunol.173.6.3901 |
| Citation | Arens R, et al. (2004) Signaling through CD70 regulates B cell activation and IgG production. J Immunol 173(6):3901-8 |
| abstractText | CD70, the cellular ligand of the TNF receptor family member CD27, is expressed transiently on activated T and B cells and constitutively on a subset of B cell chronic lymphocytic leukemia and large B cell lymphomas. In the present study, we used B cells constitutively expressing CD70 to study the functional consequences of signaling through CD70. In vitro, CD70 ligation with anti-CD70 mAbs strongly supported proliferation and cell cycle entry of B cells submitogenically stimulated with either anti-CD40 mAb, LPS, or IL-4. In this process, the cell surface receptors CD25, CD44, CD69, CD95, and GL7 were up-regulated, whereas the expression of CD21, CD62L, surface IgM (sIgM), and sIgD was decreased. Addition of CD70 mAb to low dose LPS-stimulated CD70-positive B cells strongly diminished IgG secretion and enhanced production of IgM. Signaling through CD70 on B cells was dependent on the initiation of both PI3K and MEK pathways. In vivo exposure to either CD70 mAb or the CD70 counterreceptor CD27 down-regulated CD62L and sIgM on CD70-positive B cells. CD70 signaling during T cell-dependent immune responses also decreased IgG-specific Ab titers. Together, the in vitro and in vivo data demonstrate that CD70 has potent reverse signaling properties in B cells, initiating a signaling cascade that regulates expansion and differentiation. |
