Ambrose Helen E, Wagner Simon D
Division of Investigative Sciences, Department of Haematology, Imperial College London, Hammersmith Hospital, London, UK.
Immunology. 2004 Apr;111(4):400-6. doi: 10.1111/j.1365-2567.2004.01824.x.
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.
产生高亲和力抗体需要通过体细胞超突变使抗体库多样化，随后选择那些携带最高亲和力抗体的B细胞。虽然已经鉴定出许多介导生发中心形成所需的细胞间相互作用的表面分子，但对于与细胞外基质成分（即纤连蛋白、胶原蛋白和层粘连蛋白）相互作用的重要性却知之甚少。我们证明，层粘连蛋白结合α6整合素在生发中心B细胞上表达，并在体外激活幼稚脾B细胞的过程中被诱导。在生发中心内证实存在层粘连蛋白网络。对表达α6整合素的小鼠B细胞系A20的分析表明，该分子对于与层粘连蛋白结合至关重要，并且抗α6整合素免疫球蛋白的阻断会导致黏附丧失并伴随增殖增加。这与BCL-6或Blimp-1表达的变化无关，表明α6整合素在分化中不发挥作用。
