DOCK2 couples with LEF-1 to regulate B cell metabolism and memory response

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Date
2020
DOI
10.1016/j.bbrc.2020.05.152

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Author
Yang L.
Jing Y.
Wang W.
Ying W.
Lin L.
Chang J.
Luo L.
Kang D.
Jiang P.
Liu J.
Chen Q.
Miller H.
Herrada A.A.
Kubo M.
Sun J.
Liu C.
Abstract
Dedicator of cytokinesis 2 (DOCK2) is essential for the B cell differentiation, BCR signaling and humoral immune response. However, the role of DOCK2 in the memory response of B cell is unknown. By using two DOCK2 deficient patients, we found that the memory B cells were decreased and the early activation of DOCK2 deficient memory B cells was abolished to the degree of naïve B cells due to the decreased expression of CD19 and CD21 mechanistically. Interestingly the expression of LEF-1, a negative regulator of CD21, was increased in DOCK2 deficient B cells. This was linked to the increased expression of HIF-1α and cell metabolism, which in turn affected the ER structure. Finally, the reduction of memory B cells in DOCK2 patients was due to the increased apoptosis, which might be related with the increased metabolism. © 2020
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