Dock8 regulates BCR signaling and activation of memory B cells via WASP and CD19

Blood Advances
Xiaoyu SunChaohong Liu

Abstract

Dock8 deficiency leads to immunodeficiency, and the role of Dock8 in B-cell development and function has been revealed; however, the role of DocK8 on B-cell receptor (BCR) signaling and function of memory B cells remains elusive. In this study, we generated a Dock8 knockout mouse model and collected peripheral blood mononuclear cells from Dock8 patients to study the effect of Dock8 deficiency on the BCR signaling and activation of memory B cells with confocal microscopy and total internal reflection fluorescence microscopy. The activation of key, positive upstream BCR signaling molecules, pCD19 and phosphorylated Brutons tyrosine kinase (pBtk), is reduced. Interestingly, the total protein and activated levels of Wiskott-Aldrich syndrome protein (WASP) are decreased in Dock8-deficient mouse B cells. Our previous research has shown that WASP positively regulates cd19 transcription; furthermore, we found that Dock8 regulates cd19 transcription. What we found in Dock8 patients can be a phenotype copied from Dock8 mice. The early activation of memory B cells from Dock8 patients is disrupted with reduced BCR clustering, B-cell spreading, and signalosome recruitment into the degree of naïve B cells, as well as the transition from naïv...Continue Reading

References

Oct 22, 2002·Immunity·Yue WangRobert H Carter
Jan 22, 2005·Immunological Reviews·Bodo GrimbacherJennifer M Puck
Jan 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Miguel A de la FuenteNarayanaswamy Ramesh
Sep 25, 2009·The New England Journal of Medicine·Qian ZhangHelen C Su
Oct 3, 2009·Cellular Signalling·Yuki Miyamoto, Junji Yamauchi
Dec 8, 2009·Blood·James C MulloyYi Zheng
May 15, 2012·Nature Immunology·Haifa H JabaraRaif S Geha
Sep 12, 2014·Journal of Leukocyte Biology·Sophia FriedMira Barda-Saad
Sep 7, 2016·The Journal of Clinical Investigation·Erin JanssenRaif S Geha

❮ Previous
Next ❯

Citations

Feb 12, 2020·Blood Advances·Lu HuangChaohong Liu
Dec 20, 2018·Immunological Reviews·Helen C SuAlexandra F Freeman
Jun 17, 2020·Journal of Leukocyte Biology·Yuanyuan ChenChaohong Liu
Oct 13, 2020·The Journal of Allergy and Clinical Immunology·Zuochen DuChaohong Liu
May 1, 2021·Frontiers in Cell and Developmental Biology·Madison Bolger-MunroMichael R Gold

❮ Previous
Next ❯

Related Concepts

Related Feeds

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.

B cell Differentiation

Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.