IngentaConnect Myelin protein P0-specific IgM producing monoclonal B cell lines ...

Authors: KVARNSTRÖM, M.¹; SIDOROVA, E.²; NILSSON, J.²; EKERFELT, C.¹; VRETHEM, M.³; SÖDERBERG, O.²; JOHANSSON, M.⁴; ROSÉN, A.²; ERNERUDH, J.²

Source: Clinical & Experimental Immunology, Volume 127, Number 2, February 2002 , pp. 255-262(8)

Publisher: Blackwell Publishing

Abstract:

SUMMARY

Monoclonal expansion of B cells and plasma cells, producing antibodies against `self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström's macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P₀, using beads coated with P₀. P₀-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein-Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P₀ antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5⁺ positive, although the expression declined in vitro over time. The anti-P₀ antibodies were of IgM-λ type. The antibodies belonged to the V_H3 gene family with presence of somatic mutations. The IgM reacted with P₀ and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5⁺ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P₀-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.

Keywords: monoclonal gammopathy; polyneuropathy; IgM; autoimmunity; Epstein-Barr virus; B cell clones; immunomagnetic technique

Document Type: Research article

DOI: 10.1046/j.1365-2249.2002.01739.x

Affiliations: 1: Health and Environment, Division of Clinical Immunology at Clinical Research Centre, University Hospital, Biomedicine and Surgery, 2: Division of Cell Biology and 3: Neuroscience and Locomotion, Division of Neurology, Linköping University, Linköping, Sweden 4: Division of Clinical Chemistry and

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Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS)

Myelin protein P₀-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS)