Connecting Cytoskeletal changes in B lymphocytes upon antigen exposure: a critical role for the Src-family kinase Lyn.

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ukaryotic cells assume different shapes in response to environmental stimuli. Such changes, reflect-ing alterations in the cytoskeleton of the cell, are essential for development, differentiation and func-tion. Recent studies have detailed the organised changes in the shape of lymphocytes in response to changes in their environment, particularly exposure to antigen. B and T lymphocytes reorganise their cytoskeleton following engagement of their antigen receptors (BCR in B cells, TCR in T cells). Anti-gen-driven changes in the actin cytoskeleton are regulated by Rho-family GTPases (1) while members of the ezrin/radixin/moesin (ERM) family of proteins link integral membrane proteins to the cytoskele-ton and are crucial for organizing the antigen-lymphocyte synapse (2). On the basis of published data and preliminary results, we propose that the BCR-associated tyrosine kinase Lyn plays an essential role in the transmission of information from the B cell surface to the cytoskeleton in response to anti-gen, effecting cell spreading, contraction and migration, thus determining the fate of the B cell and influencing the outcome of the immune response. The requirement for Lyn in B cell spreading and contraction in response to tethered antigen, means that exposure of Lyn-/- B cell to such antigens represents a reproducible, inducible and tractable model of aberrant cytoskeletal rearrangement within cells of a critical biological function.