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

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.

journal_name

Immunity

journal_title

Immunity

authors

Mintz MA,Felce JH,Chou MY,Mayya V,Xu Y,Shui JW,An J,Li Z,Marson A,Okada T,Ware CF,Kronenberg M,Dustin ML,Cyster JG

doi

10.1016/j.immuni.2019.05.022

subject

Has Abstract

pub_date

2019-08-20 00:00:00

pages

310-323.e7

issue

2

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(19)30242-0

journal_volume

51

pub_type

杂志文章

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