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B Cell Speed and B-FDC Contacts in Germinal Centers Determine Plasma Cell Output via Swiprosin-1/EFhd2.
Reimer, Dorothea Rakhymzhan, Asylkhan Steinmetz, Tobit Tripal, Philipp Thomas, Jana Boettcher, Martin Mougiakakos, Dimitrios Schulz, Sebastian R Urbanczyk, Sophia
Reimer, Dorothea
Rakhymzhan, Asylkhan
Steinmetz, Tobit
Tripal, Philipp
Thomas, Jana
Boettcher, Martin
Mougiakakos, Dimitrios
Schulz, Sebastian R
Urbanczyk, Sophia
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2020-08-11
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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.
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Cell Rep. 2020 Aug 11;32(6):108030. doi: 10.1016/j.celrep.2020.108030.
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en
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2211-1247
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Attribution-NonCommercial-ShareAlike 4.0 International