| Literature DB >> 32783949 |
Dorothea Reimer1, Michael Meyer-Hermann2, Asylkhan Rakhymzhan3, Tobit Steinmetz1, Philipp Tripal4, Jana Thomas1, Martin Boettcher5, Dimitrios Mougiakakos5, Sebastian R Schulz1, Sophia Urbanczyk1, Anja E Hauser6, Raluca A Niesner7, Dirk Mielenz8.
Abstract
Plasma cells secreting affinity-matured antibodies develop in germinal centers (GCs), where B cells migrate persistently and directionally over defined periods of time. How modes of GC B cell migration influence plasma cell development remained unclear. Through genetic deletion of the F-actin bundling protein Swiprosin-1/EF-hand domain family member 2 (EFhd2) and by two-photon microscopy, we show that EFhd2 restrains B cell speed in GCs and hapten-specific plasma cell output. Modeling the GC reaction reveals that increasing GC B cell speed promotes plasma cell generation. Lack of EFhd2 also reduces contacts of GC B cells with follicular dendritic cells in vivo. Computational modeling uncovers that both GC output and antibody affinity depend quantitatively on contacts of GC B cells with follicular dendritic cells when B cells migrate more persistently. Collectively, our data explain how GC B cells integrate speed and persistence of cell migration with B cell receptor affinity.Entities:
Keywords: B cell receptor; Swiprosin-1/EFhd2; actin cytoskeleton; differentiation; follicular dendritic cell; germinal center; migration; plasma cell; selection; synapse
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Year: 2020 PMID: 32783949 DOI: 10.1016/j.celrep.2020.108030
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423