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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Alpha6-integrin is expressed on germinal centre B cells and modifies growth of a B-cell line
Helen E Ambrose1, Simon D Wagner
1Division of Investigative Sciences, Department of Haematology, Imperial College London, Hammersmith Hospital, London, UK.
The production of high-affinity antibodies requires diversification of the antibody repertoire by somatic hypermutation followed by selection of those B cells bearing the highest affinity antibodies. Whilst many surface molecules that mediate the cell-cell interactions required for germinal centre formation have been identified, little is known of the importance of interactions with components of the extracellular matrix, i.e. fibronectin, collagen and laminin. We demonstrate that the laminin-binding alpha6-integrin is expressed on germinal centre B cells and is induced during the in vitro activation of naïve splenic B cells. A laminin network is demonstrated within the germinal centre. Analysis of an alpha6-integrin-expressing mouse B-cell line, A20, demonstrates that this molecule is essential for binding to laminin, and that blocking by anti-alpha6-integrin immunoglobulin causes loss of adhesion associated with an increase in proliferation. There is no correlation with changes in BCL-6 or Blimp-1 expression, suggesting that alpha6-integrin does not play a role in differentiation.
The production of high-affinity antibodies requires diversification of the antibody repertoire by somatic hypermutation followed by selection of those B cells bearing the highest affinity antibodies. Whilst many surface molecules that mediate the cell-cell interactions required for germinal centre formation have been identified, little is known of the importance of interactions with components of the extracellular matrix, i.e. fibronectin, collagen and laminin. We demonstrate that the laminin-binding alpha6-integrin is expressed on germinal centre B cells and is induced during the in vitro activation of naïve splenic B cells. A laminin network is demonstrated within the germinal centre. Analysis of an alpha6-integrin-expressing mouse B-cell line, A20, demonstrates that this molecule is essential for binding to laminin, and that blocking by anti-alpha6-integrin immunoglobulin causes loss of adhesion associated with an increase in proliferation. There is no correlation with changes in BCL-6 or Blimp-1 expression, suggesting that alpha6-integrin does not play a role in differentiation.
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