Lin Kevin B L, Freeman Spencer A, Zabetian Saba, Brugger Hayley, Weber Michele, Lei Victor, Dang-Lawson May, Tse Kathy W K, Santamaria Rene, Batista Facundo D, Gold Michael R
Department of Microbiology and Immunology, I3 and CELL Research Groups, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Immunity. 2008 Jan;28(1):75-87. doi: 10.1016/j.immuni.2007.11.019.
B lymphocytes spread and extend membrane processes when searching for antigens and form immune synapses upon contacting cells that display antigens on their surface. Although these dynamic morphological changes facilitate B cell activation, the signaling pathways underlying these processes are not fully understood. We found that activation of the Rap GTPases was essential for these changes in B cell morphology. Rap activation was important for B cell receptor (BCR)- and lymphocyte-function-associated antigen-1 (LFA-1)-induced spreading, for BCR-induced immune-synapse formation, and for particulate BCR ligands to induce localized F-actin assembly and membrane-process extension. Rap activation and F-actin assembly were also required for optimal BCR signaling in response to particulate antigens but not soluble antigens. Thus by controlling B cell morphology and cytoskeletal organization, Rap might play a key role in the activation of B cells by particulate and cell-associated antigens.
B淋巴细胞在寻找抗原时会伸展并延伸膜突起,与表面展示抗原的细胞接触时会形成免疫突触。尽管这些动态形态变化有助于B细胞活化,但这些过程背后的信号通路尚未完全了解。我们发现Rap GTP酶的激活对于B细胞形态的这些变化至关重要。Rap激活对于B细胞受体(BCR)和淋巴细胞功能相关抗原1(LFA-1)诱导的伸展、BCR诱导的免疫突触形成以及颗粒性BCR配体诱导局部F-肌动蛋白组装和膜突起延伸都很重要。Rap激活和F-肌动蛋白组装也是响应颗粒性抗原而非可溶性抗原时最佳BCR信号传导所必需的。因此,通过控制B细胞形态和细胞骨架组织,Rap可能在颗粒性和细胞相关抗原激活B细胞的过程中起关键作用。