The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20070600
The Journal of Experimental Medicine, Vol. 204, No. 10, 2259-2265
The Rockefeller University Press, 0022-1007 $30.00
© Wermeling et al.
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BRIEF DEFINITIVE REPORT

 Class A scavenger receptors regulate tolerance against apoptotic cells, and autoantibodies against these receptors are predictive of systemic lupus

Fredrik Wermeling1, Yunying Chen2, Timo Pikkarainen2, Annika Scheynius1, Ola Winqvist1, Shozo Izui3, Jeffrey V. Ravetch4, Karl Tryggvason2, and Mikael C.I. Karlsson1

1 Department of Medicine and 2 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 171 76, Sweden
3 Department of Pathology and Immunology, University of Geneva, 1211 Geneva 4, Switzerland
4 Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10021

CORRESPONDENCE Mikael C.I. Karlsson: Mikael.Karlsson{at}ki.se

Apoptotic cells are considered to be a major source for autoantigens in autoimmune diseases such as systemic lupus erythematosus (SLE). In agreement with this, defective clearance of apoptotic cells has been shown to increase disease susceptibility. Still, little is known about how apoptotic cell–derived self-antigens activate autoreactive B cells and where this takes place. In this study, we find that apoptotic cells are taken up by specific scavenger receptors expressed on macrophages in the splenic marginal zone and that mice deficient in these receptors have a lower threshold for autoantibody responses. Furthermore, antibodies against scavenger receptors are found before the onset of clinical symptoms in SLE-prone mice, and they are also found in diagnosed SLE patients. Our findings describe a novel mechanism where autoantibodies toward scavenger receptors can alter the response to apoptotic cells, affect tolerance, and thus promote disease progression. Because the autoantibodies can be detected before onset of disease in mice, they could have predictive value as early indicators of SLE.


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