DOI: 10.1084/jem.191.9.1545. Differential Regulation of B Cell Development, Activation, and Death by the Src Homology 2 Domain–Containing 5′ Inositol Phosphatase (Ship)

Differential Regulation of B Cell Development, Activation, and Death by the Src Homology 2 Domain–Containing 5′ Inositol Phosphatase (Ship)

10.1084/jem.191.9.1545

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Although the Src homology 2 domain–containing 5′ inositol phosphatase (SHIP) is a well-known mediator of inhibitory signals after B cell antigen receptor (BCR) coaggregation with the low affinity Fc receptor, it is not known whether SHIP functions to inhibit signals after stimulation through the BCR alone. Here, we show using gene-ablated mice that SHIP is a crucial regulator of BCR-mediated signaling, B cell activation, and B cell development. We demonstrate a critical role for SHIP in termination of phosphatidylinositol 3,4,5-triphosphate (PI[3,4,5]P3) signals that follow BCR aggregation. Consistent with enhanced PI(3,4,5)P3 signaling, we find that splenic B cells from SHIP-deficient mice display enhanced sensitivity to BCR-mediated induction of the activation markers CD86 and CD69. We further demonstrate that SHIP regulates the rate of B cell development in the bone marrow and spleen, as B cell precursors from SHIP-deficient mice progress more rapidly through the immature and transitional developmental stages. Finally, we observe that SHIP-deficient B cells have increased resistance to BCR-mediated cell death. These results demonstrate a central role for SHIP in regulation of BCR signaling and B cell biology, from signal driven development in the bone marrow and spleen, to activation and death in the periphery.

Bibliography

Brauweiler, A., Tamir, I., Dal Porto, J., Benschop, R. J., Helgason, C. D., Humphries, R. K., Freed, J. H., & Cambier, J. C. (2000). Differential Regulation of B Cell Development, Activation, and Death by the Src Homology 2 DomainâContaining 5â² Inositol Phosphatase (Ship). The Journal of Experimental Medicine, 191(9), 1545â1554.

Authors 8

Anne Brauweiler (first)
Idan Tamir (additional)
Joseph Dal Porto (additional)
Robert J. Benschop (additional)
Cheryl D. Helgason (additional)
R. Keith Humphries (additional)
John H. Freed (additional)
John C. Cambier (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 6:37 a.m.)
Indexed	5 months ago (March 30, 2025, 8:34 p.m.)
Issued	25 years, 4 months ago (May 1, 2000)
Published	25 years, 4 months ago (May 1, 2000)
Published Online	25 years, 4 months ago (May 1, 2000)
Published Print	25 years, 4 months ago (May 1, 2000)

Funders 0

None

BibTeX

@article{Brauweiler_2000, title={Differential Regulation of B Cell Development, Activation, and Death by the Src Homology 2 Domain–Containing 5′ Inositol Phosphatase (Ship)}, volume={191}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.191.9.1545}, DOI={10.1084/jem.191.9.1545}, number={9}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Brauweiler, Anne and Tamir, Idan and Dal Porto, Joseph and Benschop, Robert J. and Helgason, Cheryl D. and Humphries, R. Keith and Freed, John H. and Cambier, John C.}, year={2000}, month=may, pages={1545–1554} }

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  "URL": "http://dx.doi.org/10.1084/jem.191.9.1545",
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  "ISSN": [
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    "1540-9538"
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  "subject": [],
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