Abstract:
:The growth of B cell receptor (BCR) microclusters upon antigen stimulation drives B cell activation. Here, we show that PI3K-mediated PIP3 production is required for the growth of BCR microclusters. This growth is likely inhibited by PTEN and dependent on its plasma membrane binding and lipid phosphatase activities. Mechanistically, we find that PIP3-dependent recruitment and activation of a guanine nucleotide exchange factor, Dock2, is required for the sustained growth of BCR microclusters through remodeling of the F-actin cytoskeleton. As a consequence, Dock2 deficiency significantly disrupts the structure of the B cell immunological synapse. Finally, we find that primary B cells from systemic lupus erythematosus (SLE) patients exhibit more prominent BCR and PI3K microclusters than B cells from healthy controls. These results demonstrate the importance of a PI3K- and PTEN-governed PIP2 and PIP3 equilibrium in regulating the activation of B cells through Dock2-controlled growth of BCR microclusters.
journal_name
Cell Repjournal_title
Cell reportsauthors
Wang J,Xu L,Shaheen S,Liu S,Zheng W,Sun X,Li Z,Liu Wdoi
10.1016/j.celrep.2017.10.117subject
Has Abstractpub_date
2017-11-28 00:00:00pages
2541-2557issue
9issn
2211-1247pii
S2211-1247(17)31597-8journal_volume
21pub_type
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