T Cells Regulate Peripheral Naive Mature B Cell Survival by Cell-Cell Contact Mediated through SLAMF6 and SAP

• Published in: The Journal of immunology (1950) Vol. 199; no. 8; pp. 2745 - 2757
• Main Authors: Radomir, Lihi, Cohen, Sivan, Kramer, Matthias P, Bakos, Eszter, Lewinsky, Hadas, Barak, Avital, Porat, Ziv, Bucala, Richard, Stepensky, Polina, Becker-Herman, Shirly, Shachar, Idit
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 15.10.2017
• Subjects: Adaptor proteins; Animals; Antibodies, Blocking - administration & dosage; Apoptosis; B-Lymphocyte Subsets - physiology; B-Lymphocytes - physiology; Blood Cells - physiology; CD150 antigen; Cell activation; Cell Communication; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Homeostasis; Humans; Leukocyte migration; Lymphocyte receptors; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoproliferative Disorders - immunology; Macrophage migration inhibitory factor; Mice; Mice, Inbred C57BL; Mice, Knockout; Migration; RNA, Small Interfering - genetics; SAP protein; Signaling Lymphocytic Activation Molecule Associated Protein - genetics; Signaling Lymphocytic Activation Molecule Associated Protein - metabolism; Signaling Lymphocytic Activation Molecule Family - genetics; Signaling Lymphocytic Activation Molecule Family - metabolism; T-Lymphocytes - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1700557

The control of lymphoid homeostasis is the result of a very fine balance between lymphocyte production, proliferation, and apoptosis. In this study, we focused on the role of T cells in the maintenance/survival of the mature naive peripheral B cell population. We show that naive B and T cells interact via the signaling lymphocyte activation molecule (SLAM) family receptor, SLAMF6. This interaction induces cell type-specific signals in both cell types, mediated by the SLAM-associated protein (SAP) family of adaptors. This signaling results in an upregulation of the expression of the cytokine migration inhibitory factor in the T cells and augmented expression of its receptor CD74 on the B cell counterparts, consequently enhancing B cell survival. Furthermore, in X-linked lymphoproliferative disease patients, SAP deficiency reduces CD74 expression, resulting in the perturbation of B cell maintenance from the naive stage. Thus, naive T cells regulate B cell survival in a SLAMF6- and SAP-dependent manner.