Immunoglobulin light chain allelic inclusion in systemic lupus erythematosus

The principles of allelic exclusion state that each B cell expresses a single light and heavy chain pair. Here, we show that B cells with both kappa and lambda light chains (Igκ and Igλ) are enriched in some patients with the systemic autoimmune disease systemic lupus erythematosus (SLE), but not in...

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Bibliographic Details
Published in:European journal of immunology 2015-08, Vol.45 (8), p.2409-2419
Main Authors: Fraser, Louise D., Zhao, Yuan, Lutalo, Pamela M. K., D'Cruz, David P., Cason, John, Silva, Joselli S., Dunn‐Walters, Deborah K., Nayar, Saba, Cope, Andrew P., Spencer, Jo
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Allelic inclusion
Autoimmune diseases
Clinical Immunology
Female
Flow cytometry
Gene Expression Regulation - immunology
Gene Rearrangement, B-Lymphocyte, Light Chain - immunology
Humans
Igκ
Igλ
Immunoglobulin
Immunoglobulin kappa-Chains - genetics
Immunoglobulin kappa-Chains - immunology
Immunoglobulin lambda-Chains - genetics
Immunoglobulin lambda-Chains - immunology
Light
Light chain
Lupus
Lupus Erythematosus, Systemic - genetics
Lupus Erythematosus, Systemic - immunology
Lupus Erythematosus, Systemic - pathology
Middle Aged
Regular
Systemic lupus erythematosus
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Summary:The principles of allelic exclusion state that each B cell expresses a single light and heavy chain pair. Here, we show that B cells with both kappa and lambda light chains (Igκ and Igλ) are enriched in some patients with the systemic autoimmune disease systemic lupus erythematosus (SLE), but not in the systemic autoimmune disease control granulomatosis with polyangiitis. Detection of dual Igκ and Igλ expression by flow cytometry could not be abolished by acid washing or by DNAse treatment to remove any bound polyclonal antibody or complexes, and was retained after two days in culture. Both surface and intracytoplasmic dual light chain expression was evident by flow cytometry and confocal microscopy. We observed reduced frequency of rearrangements of the kappa‐deleting element (KDE) in SLE and an inverse correlation between the frequency of KDE rearrangement and the frequency of dual light chain expressing B cells. We propose that dual expression of Igκ and Igλ by a single B cell may occur in some patients with SLE when this may be a consequence of reduced activity of the KDE.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201545599