B Cell Responses: Plasmablasts Walk the Line

B Cell Responses: Plasmablasts Walk the Line

RESEARCH HIGHLIGHTS B CELL RESPONSES Plasmablasts walk the line During an adaptive immune patterns in lymph nodes. Following molecule intercellular adhesion response, long-lived antibody- immunization with specific antigen, molecule 1 (ICAM1) in plasmablast producing plasma cells are generated YFP+ cells mainly aggregated in migration. Both YFP+ and naive in T cell-dependent germinal centres. the medulla of the lymph node but B cells migrated on ICAM1-coated Plasma cells subsequently localize to could also be found in the B and glass surfaces, but only naive B cells the lymph node medullary chords, T cell zones and at the border of required Gαi-signalling for this move- but their migration to these sites has germinal centres. By contrast, naive ment. In addition, naive B cells and never been directly observed. A study B cells were predominantly localized plasma blasts had different migratory in Immunity has now reported in B cell follicles. behaviour on the ICAM1-coated sur- unique migratory behaviour for their When the migratory patterns faces; naive B cells showed frequent precursors, plasmablasts; these cells of the different populations were detachment and reattachment to the traverse the lymph node in a linear observed in situ using time-lapse substrate, but YFP+ cells migrated in manner and, surprisingly, do not two-photon intravital microscopy, a steady, amoeboid manner. + require Gαi-coupled receptor YFP cells in the medullary chords Interestingly, in assays carried signalling to migrate. were found to be mainly stationary, out in vivo and in vitro, the authors The transcriptional repressor but YFP+ cells in the follicles were reported an inverse correlation B lymphocyte-induced maturation highly motile. Naive B cells showed between cell speed and cellular YFP protein 1 (BLIMP1) is crucial for random, winding patterns of motion, intensity as BLIMP1 expression plasma cell differentiation and is an but migration of extramedullary increases during plasma cell matura- early marker of plasma cell devel- YFP+ cells was steady and linear. tion; this suggests that plasmablast opment. BLIMP1–yellow fluores- Despite having decreased migratory migration and arrest is cell auto- cent protein (BLIMP1YFP) reporter speeds compared with naive B cells, nomous. Finally, although plasma- mice expressing a transgenic B cell YFP+ cells had higher rates of dis- blasts could migrate independently receptor were therefore used to placement, consistent with these cells of Gαi-mediated signalling, PTX visualize plasma cell migration moving in a constant, linear manner. treatment at early time points follow- However, YFP+ cells did not show any ing immunization decreased plasma evidence of directional movement, cell accumulation in the medulla; suggesting that plasmablasts do not however, YFPhi cells were enriched use preformed chemotactic gradients in the B and T cell zones following to travel to the medulla. PTX treatment, suggesting that To more closely examine the plasmablast maturation is also cell role of chemokines in plasmablast autonomous. migration, the authors treated cells The authors propose a model in with pertussis toxin (PTX), which which plasmablasts seek out medul- blocks Gαi-mediated signalling and lary cords by undertaking random, prevents most chemokine-directed linear migration paths. Both the movement. Strikingly, whereas PTX migration and maturation of plasma- treatment inhibited naive B cell blasts seem to be cell autonomous, migration, PTX-treated YFP+ cells but chemokine receptor signalling continued to crawl in a persistent, may be required for plasma cell linear manner. Further experiments retention in the medulla. using the inhibitor FTY720 indicated Yvonne Bordon This image is taken from a time-lapse movie, which visualized a mouse popliteal lymph that plasmablast migration in the node during an immune response by two-photon intravital microscopy. A newly lymph node was also independent ORIGINAL RESEARCH PAPER Fooksman, D. R. generated plasmablast (green) is emigrating from a germinal centre (red), with naive of sphingosine-1-phosphate (S1P) et al. Development and migration of plasma cells B cells (blue) in the follicle. The cell track (grey) shows a highly linear path over a period of receptor signalling. The authors next in the mouse lymph node. Immunity 8 Jul 2010 75 minutes. Image courtesy of D. R. Fooksman, New York University School of Medicine, (doi:10.1016/j.immuni.2010.06.015) New York, USA. 2010 Elsevier. assessed the role of the adhesion NATURE REVIEWS | IMMUNOLOGY VOLUME 10 | AUGUST 2010 © 2010 Macmillan Publishers Limited. All rights reserved.

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