Dataset Information

The Checkpoint Regulator SLAMF3 Preferentially Prevents Expansion of Auto-Reactive B Cells Generated by Graft-vs.-Host Disease.

ABSTRACT: 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 ?SLAMF3 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 ?SLAMF3 markedly enhanced autoantibody production upon induction of cGVHD by the transfer of bm12 CD4⁺ T cells into B6 recipients. Surprisingly, ?SLAMF3 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.

SUBMITTER: Wang N

PROVIDER: S-EPMC6482334 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Checkpoint Regulator SLAMF3 Preferentially Prevents Expansion of Auto-Reactive B Cells Generated by Graft-vs.-Host Disease.

Wang Ninghai N Yigit Burcu B van der Poel Cees E CE Cuenca Marta M Carroll Michael C MC Herzog Roland W RW Engel Pablo P Terhorst Cox C

Frontiers in immunology 20190417

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-H2bm12/KhEg (bm12) CD4+ T cells into B6 WT mice. We fi ...[more]

PMID: 31057553

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Dataset Information

The Checkpoint Regulator SLAMF3 Preferentially Prevents Expansion of Auto-Reactive B Cells Generated by Graft-vs.-Host Disease.

Publications

The Checkpoint Regulator SLAMF3 Preferentially Prevents Expansion of Auto-Reactive B Cells Generated by Graft-vs.-Host Disease.

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