Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 214, Issue 11, Pages 3435-3448Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20171129
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Funding
- European Research Council under the European Union's Horizon Framework Programme [677713]
- Morris Kahn Institute for Human Immunology and Human Frontier Science Program [CDA-00023/2016]
- 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
- European Research Council (ERC) [677713] Funding Source: European Research Council (ERC)
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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.
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