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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2003-01-0180.

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Submitted January 21, 2003
Accepted May 19, 2003

Memory B cells producing somatically mutated antiphospholipid antibodies are present in normal individuals

Patricia Lieby, Anne Soley, Anne-Marie Knapp, Martine Cerutti, Jean-Marie Freyssinet, Jean-Louis Pasquali, and Thierry Martin*

Laboratoire d'Immunopathologie, INSERM EMI 0222. Institut d'Hematologie et d'Immunologie, Hopital Civil, Faculte de Medecine de Strasbourg, Strasbourg, France
Laboratoire de Pathologie Comparee, INRA/CNRS URA 2209, Saint Christol lez-Ales, France
Laboratoire d'Hematologie, Institut d'Hematologie et d'Immunologie, Hopital Civil, Faculte de Medecine de Strasbourg, Strasbourg, France

* Corresponding author; email: Thierry.Martin{at}hemato-ulp.u-strasbg.fr.

Antiphospholipid antibodies (aPL) are associated with thrombosis and recurrent abortions during autoimmune pathologies, but they are also produced in normals and during infectious diseases. To analyse the possible links between physiological and pathological aPL, it is of importance to characterize normal aPL production. We took advantage of the known tropism of Epstein-Barr virus (EBV) for B cells in general, and memory B cells in particular, during primary infectious mononucleosis (IMN) in three patients to get access to anticardiolipin (aCL) producing B cells. Flow cytometry analysis of these cells showed that, depending on the patient, 10 to 60% of IgM aCL producing B cells express the CD27 marker of memory B cells. Single cell sorting of aCL B cells, followed by single cell RT-PCR amplification of their immunoglobulin variable region genes, showed that some of these cells produce mutated forms of aCL antibodies, confirming their memory B cell origin. Considering that, during primary IMN, EBV infects and expands already preexisting memory B cells, we conclude that normal individuals have a discrete pool of aCL memory cells able to produce mutated forms of antibodies. The implications of this new information are discussed in the light of different hypothesis regarding the origin of aCL.


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