The cytosolic SHP-1 and transmembrane CD45 protein tyrosine phosphatases (PTP) play critical roles in regulating signal transduction via the B cell antigen receptor (BCR). These PTPs differ, however, in their effects on BCR function. For example, BCR-mediated mitogenesis is essentially ablated in mice lacking CD45 (CD45−), but is enhanced in SHP-1–deficient motheaten (me) and viable motheaten (mev) mice. To determine whether these PTPs act independently or coordinately in modulating the physiologic outcome of BCR engagement, we assessed B cell development and signaling in CD45-deficient mev (CD45−/SHP-1−) mice. Here we report that the CD45−/SHP-1− cells undergo appropriate induction of protein kinase activity, mitogen-activated protein kinase activation, and proliferative responses after BCR aggregation. However, BCR-elicited increases in the tyrosine phosphorylation of several SHP-1–associated phosphoproteins, including CD19, were substantially enhanced in CD45−/SHP-1−, compared to wild-type and CD45− cells. In addition, we observed that the patterns of cell surface expression of μ, δ, and CD5, which distinguish the PTP-deficient from normal mice, are largely restored to normal levels in the double mutant animals. These findings indicate a critical role for the balance of SHP-1 and CD45 activities in determining the outcome of BCR stimulation and suggest that these PTPs act in a coordinate fashion to couple antigen receptor engagement to B cell activation and maturation.
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18 August 1997
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August 18 1997
The Motheaten Mutation Rescues B Cell Signaling and Development in CD45-deficient Mice
Giovanni Pani,
Giovanni Pani
From the *Department of Immunology, ‡Department of Medicine and Molecular and Medical Genetics, University of Toronto, §The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and ‖The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada
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Katherine A. Siminovitch,
Katherine A. Siminovitch
From the *Department of Immunology, ‡Department of Medicine and Molecular and Medical Genetics, University of Toronto, §The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and ‖The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada
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Christopher J. Paige
Christopher J. Paige
From the *Department of Immunology, ‡Department of Medicine and Molecular and Medical Genetics, University of Toronto, §The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and ‖The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada
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Giovanni Pani
From the *Department of Immunology, ‡Department of Medicine and Molecular and Medical Genetics, University of Toronto, §The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and ‖The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada
Katherine A. Siminovitch
From the *Department of Immunology, ‡Department of Medicine and Molecular and Medical Genetics, University of Toronto, §The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and ‖The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada
Christopher J. Paige
From the *Department of Immunology, ‡Department of Medicine and Molecular and Medical Genetics, University of Toronto, §The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and ‖The Wellesley Hospital Research Institute, Wellesley Hospital, Toronto, Ontario, M4Y 1J3, Canada
Address correspondence to Dr. C. Paige, The Wellesley Hospital Research Institute, Wellesley Hospital, 160 Wellesley St. East, Toronto, Ontario M4Y 1J3, Canada. Phone: 416-926-7751; FAX: 416-926-5109; E-mail: [email protected]
1
Abbreviations used in this paper: BCR, B cell antigen receptor; HEL, hen egg lysozyme; HRP, horseradish peroxidase; MAP, mitogen-activated protein; me, motheaten; me v, viable motheaten; PTK, protein tyrosine kinase; PTP, protein tyrosine phosphase.
Received:
January 24 1997
Revision Received:
June 06 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (4): 581–588.
Article history
Received:
January 24 1997
Revision Received:
June 06 1997
Citation
Giovanni Pani, Katherine A. Siminovitch, Christopher J. Paige; The Motheaten Mutation Rescues B Cell Signaling and Development in CD45-deficient Mice . J Exp Med 18 August 1997; 186 (4): 581–588. doi: https://doi.org/10.1084/jem.186.4.581
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