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Journal Article

Human IgG1/IgG3 cryoglobulin suggesting lack of allelic exclusion


Lottspeich,  F.
Lottspeich, Friedrich / Protein Analysis, Max Planck Institute of Biochemistry, Max Planck Society;

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Mohanty, S., Weiner, S. M., Mentele, R., Vaith, P., Lottspeich, F., & Illges, H. (2003). Human IgG1/IgG3 cryoglobulin suggesting lack of allelic exclusion. Molecular Immunology, 39(16), 1003-1011.

Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-6BC4-E
Immunoglobulins undergoing cold-dependent precipitation are known as cryoglobulins. A type I cryoglobulin after Brouet et al. from serum of a patient with severe cutaneous vasculitis and membranoproliferative glomerulonephritis was purified by reversible temperature-dependent precipitation and analyzed using FPLC, Western blotting and peptide sequencing. The isolated cryoglobulin consisted of a single complex of a molecular weight of above 210 kDa observed under non-reducing conditions in SDS-polyacrylamide gel electrophoresis (PAGE). Under reducing conditions, this complex resolved into three bands, two of which were reminiscent of Ig heavy (HQ chains and one of Ig-light chains (LC). The FPLC-purified type I cryoglobulin showed reversible precipitation analyzed by spectrophotometry. Delineation of the peptides involved in complex formation by immunoblot analysis and peptide sequencing revealed IgG3-V(H)4/Igkappa-VkappaIII/JkappaII and IgG1/V(H)3 molecules with evidence of somatic mutation. Coomassie blue- staining suggested that molar amounts of the IgG3-heavy chain were much higher than that of the IgG1-heavy chain. Treatment with SDS and boiling did not disrupt the unusually high molecular weight Ig complex. Pre-treatment of the cryoglobulin in 6 M guadinium hydrochloride followed by gel filtration chromatography suggested covalent association of the IgG3, IgG1 and Igkappa molecules. Therefore, it might be that the cryoglobulin was produced by a single plasma B cell clone which passed immunological check-points in terms of B cell selection in the bone marrow in the absence of allelic exclusion, class switching and affinity maturation by somatic mutation. (C) 2003 Elsevier Science Ltd. All rights reserved.