Heterogeneous nuclear ribonucleoprotein P2 is an autoantibody target in mice deficient for Mer, Axl, and Tyro3 receptor tyrosine kinases

Marko Radic, Kinjal Shah, Wenguang Zhang, Qingxian Lu, Greg Lemke, George M. Hilliard

Research output: Contribution to journalArticle

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Abstract

Deficiencies in clearance of apoptotic cells predispose to the development of autoimmune disease. This is evident in mice lacking the receptor tyrosine kinases Tyro3, Axl, and Mer. Deficient mice exhibit an increased abundance of apoptotic cells in tissues and manifest diverse autoimmune conditions. To test these mice for the presence of autoantibodies to apoptotic cells, we generated spontaneous splenic B cell hybridomas and used a novel microscopy screen to detect Ab binding to apoptotic Jurkat cells. From hybridomas secreting IgG Abs reactive with apoptotic cells, we selected one that recreated the major serum specificity for apoptotic cells. The Ab LHC7.15 bound to an Ag that is differentially distributed between the nucleus and the cytoplasm in live and apoptotic cells. In late apoptotic cells, the Ag coalesces into aggregates that bleb from the cell surface. Immunopurification of the Ag, followed by mass spectrometry, identified a protein of 69 kDa whose partial sequence matched heterogeneous nuclear ribonucleoprotein P2. This multifunctional protein binds DNA, RNA, and several known ribonucleoprotein autoantigens. Our observations indicate that a ribonucleoprotein complex, formed and translocated to the cell surface in apoptosis, represents a potent stimulus for breaking tolerance and inducing systemic autoimmunity in mice with defective clearance of cell remnants.

Original languageEnglish (US)
Pages (from-to)68-74
Number of pages7
JournalJournal of Immunology
Volume176
Issue number1
DOIs
StatePublished - Jan 1 2006

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Heterogeneous-Nuclear Ribonucleoproteins
Autoantibodies
Ribonucleoproteins
Hybridomas
axl receptor tyrosine kinase
Jurkat Cells
Autoantigens
Blister
Autoimmunity
Autoimmune Diseases
Microscopy
Mass Spectrometry
Cytoplasm
Proteins
B-Lymphocytes
Immunoglobulin G
RNA

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Heterogeneous nuclear ribonucleoprotein P2 is an autoantibody target in mice deficient for Mer, Axl, and Tyro3 receptor tyrosine kinases. / Radic, Marko; Shah, Kinjal; Zhang, Wenguang; Lu, Qingxian; Lemke, Greg; Hilliard, George M.

In: Journal of Immunology, Vol. 176, No. 1, 01.01.2006, p. 68-74.

Research output: Contribution to journalArticle

Radic, Marko ; Shah, Kinjal ; Zhang, Wenguang ; Lu, Qingxian ; Lemke, Greg ; Hilliard, George M. / Heterogeneous nuclear ribonucleoprotein P2 is an autoantibody target in mice deficient for Mer, Axl, and Tyro3 receptor tyrosine kinases. In: Journal of Immunology. 2006 ; Vol. 176, No. 1. pp. 68-74.
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