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

Irina Zaretsky; Ofir Atrakchi; Roei D Mazor; Liat Stoler-Barak; Adi Biram; Sara W Feigelson; Alexander D Gitlin; Britta Engelhardt; Ziv Shulman

doi:10.1084/jem.20171129

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.

Authors

Irina Zaretsky¹, Ofir Atrakchi¹, Roei D Mazor¹, Liat Stoler-Barak¹, Adi Biram¹, Sara W Feigelson¹, Alexander D Gitlin², Britta Engelhardt³, Ziv Shulman⁴

Affiliations

¹ Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
² Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.
³ Theodor Kocher Institute, University of Bern, Bern, Switzerland.
⁴ Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel [email protected].

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