ICAMs support B cell interactions with T follicular helper cells and promote clonal selection

J Exp Med. 2017 Nov 6;214(11):3435-3448. doi: 10.1084/jem.20171129. Epub 2017 Sep 22.

Abstract

The germinal center (GC) reaction begins with a diverse and expanded group of B cell clones bearing a wide range of antibody affinities. During GC colonization, B cells engage in long-lasting interactions with T follicular helper (Tfh) cells, a process that depends on antigen uptake and antigen presentation to the Tfh cells. How long-lasting T-B interactions and B cell clonal expansion are regulated by antigen presentation remains unclear. Here, we use in vivo B cell competition models and intravital imaging to examine the adhesive mechanisms governing B cell selection for GC colonization. We find that intercellular adhesion molecule 1 (ICAM-1) and ICAM-2 on B cells are essential for long-lasting cognate Tfh-B cell interactions and efficient selection of low-affinity B cell clones for proliferative clonal expansion. Thus, B cell ICAMs promote efficient antibody immune response by enhancement of T cell help to cognate B cells.

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology*
  • Cell Adhesion Molecules / metabolism
  • Cell Communication / genetics
  • Cell Communication / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Clone Cells / immunology
  • Clone Cells / metabolism
  • Flow Cytometry
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • Antigens, CD
  • Cell Adhesion Molecules
  • ICAM-2 protein, mouse
  • Intercellular Adhesion Molecule-1