Bruton's Tyrosine Kinase Is Not Essential for B Cell Survival beyond Early Developmental Stages

The Journal of Immunology : Official Journal of the American Association of Immunologists
Lindsay E NyhoffPeggy L Kendall

Abstract

Bruton's tyrosine kinase (Btk) is a crucial regulator of B cell signaling and is a therapeutic target for lymphoma and autoimmune disease. BTK-deficient patients suffer from humoral immunodeficiency, as their B cells fail to progress beyond the bone marrow. However, the role of Btk in fully developed, mature peripheral B cells is not well understood. Analysis using BTK inhibitors is complicated by suboptimal inhibition, off-target effects, or failure to eliminate BTK's adaptor function. Therefore a Btkflox/Cre-ERT2 mouse model was developed and used to excise Btk after B cell populations were established. Mice lacking Btk from birth are known to have reduced follicular (FO) compartments, with expanded transitional populations, suggesting a block in development. In adult Btkflox/Cre-ERT2 mice, Btk excision did not reduce FO B cells, which persisted for weeks. Autoimmune-prone B1 cells also survived conditional Btk excision, contrasting their near absence in global Btk-deficient mice. Therefore, Btk supports BCR signaling during selection into the FO and B1 compartments, but is not needed to maintain these cell populations. B1-related natural IgM levels remained normal, contrasting global Btk deficiency, but B cell proliferation ...Continue Reading

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Citations

Apr 17, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Philipp HaselmayerRoland Grenningloh
Feb 6, 2020·Annual Review of Immunology·Adrian C Hayday, Pierre Vantourout
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Nov 21, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lindsay E NyhoffPeggy L Kendall

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