B Cell Speed and B-FDC Contacts in Germinal Centers Determine Plasma Cell Output via Swiprosin-1/EFhd2

• Published in: Cell reports (Cambridge) Vol. 32; no. 6; p. 108030
• Main Authors: Reimer, Dorothea, Meyer-Hermann, Michael, Rakhymzhan, Asylkhan, Steinmetz, Tobit, Tripal, Philipp, Thomas, Jana, Boettcher, Martin, Mougiakakos, Dimitrios, Schulz, Sebastian R., Urbanczyk, Sophia, Hauser, Anja E., Niesner, Raluca A., Mielenz, Dirk
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.08.2020; Elsevier
• Subjects: actin cytoskeleton; B cell receptor; differentiation; follicular dendritic cell; germinal center; migration; plasma cell; selection; Swiprosin-1/EFhd2; synapse; actin cytoskeleton; differentiation; selection; Swiprosin-1/EFhd2; migration; germinal center; synapse; follicular dendritic cell; B cell receptor; plasma cell
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108030

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. [Display omitted] •EFhd2 limits migration of GC B cells and hapten-specific immunity•Fast GC B cells are selected earlier and prone to differentiate•EFhd2 fosters contacts of GC B cells with follicular dendritic cells•Contact of fast GC B cells with follicular dendritic cells is decisive Reimer et al. show that EFhd2 restricts migration of germinal center B cells and hapten-specific immunity. Selection of speedy germinal center B cells occurs earlier and they are more likely to differentiate. EFhd2 supports contact of germinal center B cells with follicular dendritic cells, enabling successful competition of rapidly migrating germinal center B cells.