Paolo Pierobon

How B cells capture, process and present antigens: a crucial role for cell polarity

B cells are key components of the adaptive immune response. Their differentiation into either specific memory B cells or antibody-secreting plasma cells is a consequence of activation steps that involve the processing and presentation of antigens. The engagement of B cell receptors by surface-tethered antigens leads to the formation of an immunological synapse that coordinates cell signalling events and that promotes antigen uptake for presentation on MHC class II molecules. In this Review, we discuss membrane trafficking and the associated molecular mechanisms that are involved in antigen extraction and processing at the B cell synapse, and we highlight how B cells use cell polarity to coordinate the complex events that ultimately lead to efficient humoral responses.

Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA–mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42–Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4–MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function.

Quantum dots to tail single bio-molecules inside living cells.

In the last two decades, the single particle and single molecule approach became more and more popular to investigate the activity and the mechano-chemical properties of biological molecules. The inherent limit of these assays was that the molecules of interest were observed in vitro, out of their natural environment, the cell. Several recent works have shown the possibility to overcome this limit, to extend this approach to living cells and to observe the details of many cellular processes at the molecular level. In this review we discuss the use of semiconductor quantum dots to perform single particle and single molecule tracking in the cell. We refer to other articles for the technical aspects of this method. Here, after an introduction on the advantages provided by these nanoparticles, we restrict ourselves to some examples, mainly related to intracellular transport and molecular motor activity. These will illustrate the important role played by semiconductor quantum dots as fluorescent nano-reporters in in cell single molecule approach in modern biology and biophysics.

Cdc42 controls the dilation of the exocytotic fusion pore by regulating membrane tension

On exocytosis, membrane fusion starts with the formation of a narrow fusion pore that must expand to allow the release of secretory compounds. The GTPase Cdc42 promotes fusion pore dilation in neuroendocrine cells by controlling membrane tension.

Polarity protein Par3 controls B-cell receptor dynamics and antigen extraction at the immune synapse

Ancestral polarity protein Par3 is crucial for the polarization of B-cells toward a tethered antigen. This process is needed by these lymphocytes to uptake and process the antigen to mount the adaptive immune response.

Dynamics of the membrane-cytoskeleton interface in MHC class II-restricted antigen presentation.

Antigen presentation refers to the ability of cells to show MHC‐associated determinants to T lymphocytes, leading to their activation. MHC class II molecules mainly present peptide‐derived antigens that are internalized by endocytosis in antigen‐presenting cells (APCs). Here, we describe how the interface between cellular membranes and the cytoskeleton regulates the various steps that lead to the presentation of exogenous antigens on MHC class II molecules in the two main types of APCs: dendritic cells (DCs) and B lymphocytes. This includes antigen uptake, processing, APC migration, and APC–T cell interactions. We further discuss how the interaction between APC‐specific molecules and cytoskeleton elements allows the coordination of antigen presentation and cell migration in time and space.

Traffic of Molecular Motors: From Theory to Experiments

Intracellular transport along microtubules or actin filaments, powered by molecular motors such as kinesins, dyneins or myosins, has been recently modeled using one-dimensional driven lattice gases. We discuss some generalizations of these models, that include extended particles and defects. We investigate the feasibility of single molecule experiments aiming to measure the average motor density and to locate the position of traffic jams by mean of a tracer particle. Finally, we comment on preliminary single molecule experiments performed in living cells.

To use or not to use the force: How B lymphocytes extract surface-tethered antigens.

Pierobon and Lennon-Duménil highlight recent findings on how the mechanical properties of membranes affect uptake of surface-tethered antigen by B lymphocytes.

Corrigendum: Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

Corrigendum: Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells