Immunoglobulin light chain allelic inclusion in systemic lupus erythematosus

TY - JOUR

T1 - Immunoglobulin light chain allelic inclusion in systemic lupus erythematosus

AU - Fraser, Louise D.

AU - Zhao, Yuan

AU - Lutalo, Pamela M K

AU - D’Cruz, David

AU - Cason, John

AU - Silva O'Hare, Joselli

AU - Dunn-Walters, Deborah

AU - Nayar, Saba

AU - Cope, Andrew P.

AU - Spencer, Jo

PY - 2015/8

Y1 - 2015/8

N2 - 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.

AB - 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.

KW - Allelic inclusion

KW - Igκ

KW - Igλ

KW - Immunoglobulin

KW - Light chain

KW - Systemic lupus erythematosus

UR - http://www.scopus.com/inward/record.url?scp=84932611418&partnerID=8YFLogxK

U2 - 10.1002/eji.201545599

DO - 10.1002/eji.201545599

M3 - Article

SN - 0014-2980

VL - 45

SP - 2409

EP - 2419

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 8

ER -