Protein Phosphatase 2A, a Serine/Threonine Phosphatase, Is Essential for Optimal B Cell Function

Esra Meidan¹, Hao Li², Christina Ioannidis³, Wenliang Pan³, Noe Rodriguez Rodriguez⁴, Jose Crispin⁴, Sokratis Apostolidis⁵, John Manis⁶, Amir Sharabi⁷, Maria G. Tsokos³ and George C Tsokos⁸, ¹Division of Immunology, Boston Children's Hospital, Boston, MA, ²Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, ³Beth Israel Deaconess Medical Center, Boston, MA, ⁴Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico, ⁵Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, ⁶Boston Children's Hospital, Boston, MA, ⁷Department of Rheumatology, Beth Israel Deaconess Medical Center, Boston, MA, ⁸Division of Rheumatology, Department of Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, Boston, MA

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: B cells and SLE

Session Information

Date: Sunday, October 21, 2018

Title: B Cell Biology and Targets in Autoimmune and Inflammatory Disease Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase ubiquitously expressed in eukaryotic cells. PP2A levels and activity are increased in T cells from patients with systemic lupus erythematosus and account for certain aspects of their aberrant function. We asked whether PP2A is similarly involved in the control of B cell function in lupus.

Methods:

To understand the contribution of PP2A to B cell function, we generated a Cd19^CrePpp2r1a^flox/flox(flox/flox) mouse which lacks functional PP2A specifically in B cells along with Cd19^CrePpp2r1a^WT/WT(control) mice. B cells were isolated from lupus-prone Mrl.lpr, SLE1.2.3 and B6.lpr mice to study the activity and protein levels of PP2A. Flow cytometry was performed in peripheral blood mononuclear cells of 15 patients with systemic lupus erythematosus and age, sex and race-matched healthy controls to measure the level of catalytic subunit of PP2A.

Results:

We found that in vitro activated B cells by CpG, anti-IgM and anti-CD40 display increased PP2A activity. Flox/flox mice displayed decreased spontaneous germinal center B cells and decreased serum immunoglobulin levels compared to control mice. Immunization of flox/flox mice with sheep red blood cells resulted in decreased germinal center formation and immunization with T-dependent and T-independent antigens resulted in impaired antigen specific immunoglobulin production. In vitro stimulation of flox/flox B cells with anti-CD40/IL-4 and CpG/IL-4 similarly resulted in decreased immunoglobulin production. B cells from lupus-prone mice showed increased levels of PP2A and PP2A activity. B cells from patients with systemic lupus erythematosus expressed increased levels of PP2A.

Conclusion:

Our results demonstrate that PP2A is required for optimal B cell function and contributes to increased B cell activity in systemic autoimmunity.

Disclosure: E. Meidan, None; H. Li, None; C. Ioannidis, None; W. Pan, None; N. Rodriguez Rodriguez, None; J. Crispin, None; S. Apostolidis, None; J. Manis, None; A. Sharabi, None; M. G. Tsokos, None; G. C. Tsokos, Janssen Research & Development, LLC, 2.

To cite this abstract in AMA style:

Meidan E, Li H, Ioannidis C, Pan W, Rodriguez Rodriguez N, Crispin J, Apostolidis S, Manis J, Sharabi A, Tsokos MG, Tsokos GC. Protein Phosphatase 2A, a Serine/Threonine Phosphatase, Is Essential for Optimal B Cell Function [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/protein-phosphatase-2a-a-serine-threonine-phosphatase-is-essential-for-optimal-b-cell-function/. Accessed .

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