| First Author | Wang N | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 831 | PubMed ID | 31057553 |
| Mgi Jnum | J:281782 | Mgi Id | MGI:6380740 |
| Doi | 10.3389/fimmu.2019.00831 | Citation | Wang N, et al. (2019) The Checkpoint Regulator SLAMF3 Preferentially Prevents Expansion of Auto-Reactive B Cells Generated by Graft-vs.-Host Disease. Front Immunol 10:831 |
| abstractText | Absence of the mouse cell surface receptor SLAMF3 in SLAMF3-/- mice suggested that this receptor negatively regulates B cell homeostasis by modulating activation thresholds of B cell subsets. Here, we examine whether anti-SLAMF3 affects both B and T cell subsets during immune responses to haptenated ovalbumin [NP-OVA] and in the setting of chronic graft vs. host disease (cGVHD) induced by transferring B6.C-H2 (bm12)/KhEg (bm12) CD4(+) T cells into B6 WT mice. We find that administering alphaSLAMF3 to NP-OVA immunized B6 mice primarily impairs antibody responses and Germinal center B cell [GC B] numbers, whilst CXCR5(+), PD-1(+), and ICOS(+) T follicular helper (TFH) cells are not significantly affected. By contrast, administering alphaSLAMF3 markedly enhanced autoantibody production upon induction of cGVHD by the transfer of bm12 CD4(+) T cells into B6 recipients. Surprisingly, alphaSLAMF3 accelerated both the differentiation of GC B and donor-derived TFH cells initiated by cGVHD. The latter appeared to be induced by decreased numbers of donor-derived Treg and T follicular regulatory (TFR) cells. Collectively, these data show that control of anti-SLAMF3-induced signaling is requisite to prevent autoantibody responses during cGVHD, but reduces responses to foreign antigens. |
