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.
Original language | English |
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Pages (from-to) | 3435-3448 |
Number of pages | 14 |
Journal | Journal of Experimental Medicine |
Volume | 214 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Nov 2017 |
Funding
We thank M.C. Nussenzweig (Rockefeller University) for discussions and mice and Urban Deutsch (University of Bern) for ICAM-1/2−/− BM cells. We thank Matteo Iannacone (San Raffaele Institute) for providing VSV. This project has received funding from the European Research Council under the European Union’s Horizon 2020 Framework Programme (grant agreement 677713). Supported by research grants from the Morris Kahn Institute for Human Immunology and Human Frontier Science Program (CDA-00023/2016), Azrieli Foundation, and Rising Tide Foundation. Supported by grants from the Benoziyo Endowment Fund for the Advancement of Science, the Sir Charles Clore Research Prize, Comisaroff Family Trust, the Irma and Jacques Ber-Lehmsdorf Foundation, the Gerald O. Mann Charitable Foundation, and the David M. Polen Charitable Trust. The authors declare no competing financial interests. Author contributions: I. Zaretsky, O. Atrakchi, R.D. Mazor, L. Stoler-Barak, and A. Biram planned and performed experiments. S.W. Feigelson provided assistance with mouse husbandry and experiments. A.D. Gitlin provided assistance with experiments and manuscript writing. B. Engelhardt provided mouse models. Z. Shulman planned experiments and wrote the manuscript.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology