The HVEM-BTLA Axis Restrains T Cell Help to Germinal Center B Cells and Functions as a Cell-Extrinsic Suppressor in Lymphomagenesis

浏览次数:8 分享:
  • Immunity
  • 26.3
  • 2019 Aug 20;51(2):310-323.e7.
  • Mouse
  • 流式
  • 免疫/内分泌
  • 免疫/内分泌
  • T细胞
  • 淋巴瘤
  • CD19,CD196 (CCR6),CD4,CD95,Vα2 TCR
  • doi: 10.1016/j.immuni.2019.05.022.

Abstract

The tumor necrosis factor receptor superfamily member HVEM is one of the most frequently mutated surface proteins in germinal center (GC)-derived B cell lymphomas. We found that HVEM deficiency increased B cell competitiveness during pre-GC and GC responses. The immunoglobulin (Ig) superfamily protein BTLA regulated HVEM-expressing B cell responses independently of B-cell-intrinsic signaling via HVEM or BTLA. BTLA signaling into T cells through the phosphatase SHP1 reduced T cell receptor (TCR) signaling and preformed CD40 ligand mobilization to the immunological synapse, thus diminishing the help delivered to B cells. Moreover, T cell deficiency in BTLA cooperated with B cell Bcl-2 overexpression, leading to GC B cell outgrowth. These results establish that HVEM restrains the T helper signals delivered to B cells to influence GC selection outcomes, and they suggest that BTLA functions as a cell-extrinsic suppressor of GC B cell lymphomagenesis.
金课堂之文献解析 文献原文请点击

技术文章 更多

    研究领域 更多

      热点文献