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A VH4-34⁺ myeloma protein with weak autoreactivity

From the Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway (MF, KMT, BB); National Institute for Biological Standards and Control, Potters Bar, UK (SJT); Cancer Sciences Division, University of Southampton, Southampton, UK (SSS); Section of Hematology, Medical Department, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway (TGD)

Correspondence: Keith M. Thompson, Institute of Immunology, Rikshospitalet, N-0027 Oslo, Norway. E-mail: keith.thompson{at}medisin.uio.no/ bjarne.bogen{at}medisin.uio.no.

It has been suggested that VH4-34 gene segment expression is counter-selected in multiple myeloma (MM) due to a self-tolerance mechanism. We cloned and sequenced a VH4-34 gene segment from bone marrow mononuclear cells of a stage III MM patient. We show that VH4-34 was expressed by the serum IgA myeloma (M)-protein, as demonstrated by reactivity with the VH4-34 specific 9G4 mAb and mass spectrometry (MS). The M-protein had weak reactivity with nuclei. These results demonstrate that VH4-34 may be expressed in secreted IgA M-protein with weak autoreactivity. Thus, counter-selection of VH4-34 is pronounced but not absolute in MM. Mechanisms of how VH4-34 can occasionally be expressed in MM and clinical implications are discussed.

Key words: VH4-34, myeloma protein, autoreactivity.