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

Author:

Zaretsky Irina1ORCID,Atrakchi Ofir1,Mazor Roei D.1ORCID,Stoler-Barak Liat1,Biram Adi1ORCID,Feigelson Sara W.1,Gitlin Alexander D.2,Engelhardt Britta3,Shulman Ziv1ORCID

Affiliation:

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

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.

Funder

European Research Council

Horizon 2020 Framework Programme

Morris Kahn Institute for Human Immunology

Human Frontier Science Program

Azrieli Foundation

Rising Tide Foundation

Benoziyo Endowment Fund for the Advancement of Science

Sir Charles Clore Research Prize

Comisaroff Family Trust

Irma and Jacques Ber-Lehmsdorf Foundation

Gerald O. Mann Charitable Foundation

David M. Polen Charitable Trust

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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