Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.immuni.2019.05.022

Type

Journal article

Journal

Immunity

Publication Date

08/2019

Volume

51

Pages

310 - 323.e7

Addresses

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.

Keywords

Germinal Center, B-Lymphocytes, T-Lymphocytes, Helper-Inducer, Animals, Mice, Transgenic, Mice, Knockout, Mice, Receptors, Immunologic, Receptors, Antigen, T-Cell, Proto-Oncogene Proteins c-bcl-2, Lymphocyte Activation, Paracrine Communication, Signal Transduction, Cell Proliferation, Receptors, Tumor Necrosis Factor, Member 14, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Immunological Synapses