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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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Blood, 1 October 2003, Vol. 102, No. 7, pp. 2459-2465

HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

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

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

From the Laboratoire d'Immunopathologie, Institut National de la Santé etdela Recherche Médicale (INSERM) EMI 0222, Institut d'Hématologie et d'Immunologie, Hôpital Civil, Faculté deMédecine de Strasbourg, Strasbourg, France; Laboratoire de Pathologie Comparée, Institut National pour la Recherche Agronomique/Institut National pour la Recherche Scientifique (INRA/CNRS) URA2209, Saint Christol lez-Alès, France; Laboratoire d'Hématologie, Institut d'Hématologie et d'Immunologie, Hôpital Civil, Faculté deMédecine de Strasbourg, Strasbourg, France; and the Unité 143 INSERM, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.

Antiphospholipid antibodies (aPLs) are associated with thrombosis and recurrent abortions during autoimmune pathologies, but they are also produced in healthy individuals and during infectious diseases. To analyze the possible links between physiologic and pathologic aPLs, 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 3 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 immunoglobulin M (IgM) aCL-producing B cells express the CD27 marker of memory B cells. Single cell sorting of aCL B cells, followed by single cell reverse transcription-polymerase chain reaction (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 pre-existing memory B cells, we conclude that healthy 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 light of different hypotheses regarding the origin of aCL. (Blood. 2003;102:2459-2465)


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