Contribution of secondary Igkappa rearrangement to primary immunoglobulin repertoire diversification.
Abs reactive to DNA and DNA/histone complexes are a distinguished characteristic of primary immunoglobulin repertoires in autoimmune B6.MRL-Faslprand MRL/MpJ-Faslprmice. These mice are defective in Fas receptor, which is critical for the apoptosis of autoreactive B cells by an extrinsic pathway. In the present study, we explored the possibility that bone marrow small pre-B and immature B cells from adult B6.MRL-Faslprmice and MRL/MpJ-Faslprmice respectively, which contain autoreactive B-cell antigen receptors (BCR) and manifest autoimmune syndromes, exhibit enhanced receptor editing patterns. Indeed, FASlprpre B and immature B cells were shown to possess more ongoing replacements of non-productive (nP) than productive (P) primary VκJκ rearrangements. Significantly, the P vs nP ratios of these replaced primary rearrangements were 1:2, thus indicating that κ light-chain production appears not to inhibit secondary rearrangements. In addition, we identified multiple atypical rearrangements, such as Vκ cRS (cryptic recombination signals) cleavages. These results suggest that the onset of light chain secondary rearrangements persists similarly as a non-selected mode and independent of BCR autoreactivity during certain developmental windows of bone marrow B cells in lupus-prone mice and control, and leads us to propose the function of secondary, de novo Igκ rearrangements to increase BCR diversity.
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
Shufang
S
Li
Tianjin Entry-Exit Inspection and Quarantine Bureau, Tianjin 300308, China.
Wei
W
Liu
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
Yinghui
Y
Li
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
Shaorong
S
Zhao
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
Can
C
Liu
Collage of Life Science, Nankai University, Tianjin, 300071, China.
Mengyun
M
Hu
Department of Neurology, Huanhu Hospital, Tianjin 300060, China.
Wei
W
Yue
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
Yanhua
Y
Liu
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
Yue
Y
Wang
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China.
Rongcun
R
Yang
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China. Electronic address: rxiang@nankai.edu.cn.
Rong
R
Xiang
Department of Immunology, School of Medicine, Nankai University, Tianjin 300071, China. Electronic address: liufeifei@nankai.edu.cn.
Feifei
F
Liu
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016133:Polymerase Chain Reaction; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*
D007145:Immunoglobulin kappa-Chains; D011947:Receptors, Antigen, B-Cell
B cell; Development; Secondary Igkappa rearrangement; VDJ recombination