The role of the Cytoskeleton in lymphocyte activation

​Description of research

B cells constitute an essential part of the adaptive immune system by producing antibodies, which neutralize toxins and infected or malignant cells. Our projects focus on understanding the molecular regulation of B cell activation and, specifically, unveiling the role of the actin cytoskeleton in this process. Tightly regulated, yet robust triggering of B cells is critical for mounting of humoral immune response upon infection or vaccination. Diminished B cell activation leads to a variety of immune deficiencies and, on the other hand, lowered activation threshold can lead to autoimmune disorders. Furthermore, transformations in the B cell signaling pathways may lead to malignant growth and development of lymphoma.
We are particularly interested in the role of the actin cytoskeleton in different stages of B cell activation. How the remodeling of the cytoskeleton is orches-trated in response to the antigen receptor signaling? How specific features of this multifaceted structure, such as the sub-membranous actin cortex, can directly influence the receptor signaling and activation potential of the cell? How are the membrane-cytoskeleton interfaces coordinated to allow anti-gen internalization and intracellular processing ultimately leading to antigen peptide-MHCII complex presentation and T cell help? To answer these ques-tions, we take advantage of advanced microscopic methods, such as super-resolution microscopy, in combination with modern cell biological, molecular biological and biochemical methods.

Members of the resarch group

Luqman Awoniyi, MSc
Marika Jaakkola, MSc
Elina Kuokkanen, PhD
Alexey Sarapulov, MSc
Vid Šuštar, PhD
Hanna-Maria Judin, BSc
Sara Hernandez-Perez, BSc

Selected Publications

Kuokkanen E, Šuštar V, Mattila PK. (2015) Molecular control of B cell activation and immunological synapse formation. Traffic; 16:311-26.
Mattila PK, Feest C, Depoil D, Treanor B, Montaner B, Otipoby KL, Carter R, Justement LB, Bruckbauer A, Batista FD. (2013) The actin and tetraspanin networks organize receptor nanoclusters to regulate B cell receptor-mediated signaling. Immunity. 38:461-74.
Saarikangas J*, Mattila PK*, Varjosalo M, Bovellan M, Hakanen J, et al. & Lappalainen P. (2011) Missing-in-metastasis (MIM/MTSS1) Promotes Actin Assembly at Intercellular Junctions and Is Required for Kidney Epithelia Integrity. Journal of Cell Science; 124:1245-55. *equal contribution.
Mattila PK, Lappalainen P. (2008) Filopodia: molecular architecture and cellular functions. Nature Reviews Molecular Cell Biology; 9:446-54.
Mattila PK, Pykäläinen A, Saarikangas J, Paavilainen VO, Vihinen H, Jokitalo E, Lappalainen P. (2007) Missing-In-Metastasis (MIM) and IRSp53 deform PI(4,5)P2-rich membranes in an inverse BAR-like mechanism. Journal of Cell Biology; 176:953-64.



 Docent Pieta Mattila