SLAM family receptors control pro-survival effectors in germinal center B cells to promote humoral immunity

J Exp Med. 2021 Mar 1;218(3):e20200756. doi: 10.1084/jem.20200756.

Abstract

Expression of the signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is critical for the germinal center (GC) reaction and T cell-dependent antibody production. However, when SAP is expressed normally, the role of the associated SLAM family receptors (SFRs) in these processes is nebulous. Herein, we established that in the presence of SAP, SFRs suppressed the expansion of the GC reaction but facilitated the generation of antigen-specific B cells and antibodies. SFRs favored the generation of antigen-reactive B cells and antibodies by boosting expression of pro-survival effectors, such as the B cell antigen receptor (BCR) and Bcl-2, in activated GC B cells. The effects of SFRs on the GC reaction and T cell-dependent antibody production necessitated expression of multiple SFRs, both in T cells and in B cells. Hence, while in the presence of SAP, SFRs inhibit the GC reaction, they are critical for the induction of T cell-mediated humoral immunity by enhancing expression of pro-survival effectors in GC B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / metabolism
  • Antibody Formation / immunology
  • Antigens, Helminth / metabolism
  • Apoptosis
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • Bone Marrow / metabolism
  • Cell Count
  • Cell Cycle
  • Cell Proliferation
  • Cell Survival
  • Dose-Response Relationship, Immunologic
  • Germinal Center / cytology*
  • Immunity, Humoral*
  • Immunization
  • Immunoglobulin Class Switching
  • Immunologic Memory
  • Mice
  • Mice, Knockout
  • Nematospiroides dubius / physiology
  • Plasma Cells / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Signaling Lymphocytic Activation Molecule Family / deficiency
  • Signaling Lymphocytic Activation Molecule Family / metabolism*
  • Somatic Hypermutation, Immunoglobulin
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Vaccination

Substances

  • Antibodies
  • Antigens, Helminth
  • Proto-Oncogene Proteins c-bcl-2
  • Signaling Lymphocytic Activation Molecule Family