Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients

Judith Fraussen; Kathleen Vrolix; Nele Claes; Pilar Martinez-Martinez; Mario Losen; Raymond Hupperts; Bart Van Wijmeersch; Mercedes Espino; Luisa M. Villar; Marc H. De Baets; Piet Stinissen; Veerle Somers

doi:10.1016/j.jneuroim.2013.05.002

Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients

Judith Fraussen, Kathleen Vrolix, Nele Claes, Pilar Martinez-Martinez, Mario Losen, Raymond Hupperts, Bart Van Wijmeersch, Mercedes Espino, Luisa M. Villar, Marc H. De Baets, Piet Stinissen, Veerle Somers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

6 Citations (Web of Science)

Abstract

We studied Ig heavy chain (VDJ) sequences and antigen reactivity of 412 immortalized B cell lines from the peripheral blood of 10 multiple sclerosis (MS) patients, 4 clinically isolated syndrome (CIS) patients and 6 healthy controls (HCs). 78/238 (32.8%) MS and CIS B cell lines were part of 9 clonally expanded B cell populations, of which 5 were present in multiple patients. Increased VH1 gene family usage was evidenced for MS B cells, with 29.2% expressing VH1-69. Affinity maturation in MS and CIS was indicated by increased Ig VDJ mutations. Autoantibody producing B cells reactive to intracellular antigens were significantly higher in MS (25%) and CIS (28%) patients than in HCs (5%), including 3/9 expanded B cell clones. Specificity for phosphatidylcholine was observed for 1/9 B cell clones. These findings indicate clonally expanded autoreactive B cells with affinity maturation in the peripheral blood in MS and CIS.

Original language	English
Pages (from-to)	98-107
Journal	Journal of Neuroimmunology
Volume	261
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2013.05.002
Publication status	Published - 15 Aug 2013

Keywords

Multiple sclerosis
Clinically isolated syndrome
B cell immortalization
Complementarity determining region 3
Clonal B cell expansion
Autoreactivity

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10.1016/j.jneuroim.2013.05.002

Cite this

Fraussen, J., Vrolix, K., Claes, N., Martinez-Martinez, P., Losen, M., Hupperts, R., Van Wijmeersch, B., Espino, M., Villar, L. M., De Baets, M. H., Stinissen, P., & Somers, V. (2013). Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients. Journal of Neuroimmunology, 261(1-2), 98-107. https://doi.org/10.1016/j.jneuroim.2013.05.002

@article{059d1782d43f45d89fba9994d0ba71d9,

title = "Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients",

abstract = "We studied Ig heavy chain (VDJ) sequences and antigen reactivity of 412 immortalized B cell lines from the peripheral blood of 10 multiple sclerosis (MS) patients, 4 clinically isolated syndrome (CIS) patients and 6 healthy controls (HCs). 78/238 (32.8%) MS and CIS B cell lines were part of 9 clonally expanded B cell populations, of which 5 were present in multiple patients. Increased VH1 gene family usage was evidenced for MS B cells, with 29.2% expressing VH1-69. Affinity maturation in MS and CIS was indicated by increased Ig VDJ mutations. Autoantibody producing B cells reactive to intracellular antigens were significantly higher in MS (25%) and CIS (28%) patients than in HCs (5%), including 3/9 expanded B cell clones. Specificity for phosphatidylcholine was observed for 1/9 B cell clones. These findings indicate clonally expanded autoreactive B cells with affinity maturation in the peripheral blood in MS and CIS. ",

keywords = "Multiple sclerosis, Clinically isolated syndrome, B cell immortalization, Complementarity determining region 3, Clonal B cell expansion, Autoreactivity",

author = "Judith Fraussen and Kathleen Vrolix and Nele Claes and Pilar Martinez-Martinez and Mario Losen and Raymond Hupperts and {Van Wijmeersch}, Bart and Mercedes Espino and Villar, {Luisa M.} and {De Baets}, {Marc H.} and Piet Stinissen and Veerle Somers",

year = "2013",

month = aug,

day = "15",

doi = "10.1016/j.jneuroim.2013.05.002",

language = "English",

volume = "261",

pages = "98--107",

journal = "Journal of Neuroimmunology",

issn = "0165-5728",

publisher = "Elsevier",

number = "1-2",

}

Fraussen, J, Vrolix, K, Claes, N, Martinez-Martinez, P , Losen, M , Hupperts, R, Van Wijmeersch, B, Espino, M, Villar, LM, De Baets, MH, Stinissen, P & Somers, V 2013, 'Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients', Journal of Neuroimmunology, vol. 261, no. 1-2, pp. 98-107. https://doi.org/10.1016/j.jneuroim.2013.05.002

TY - JOUR

T1 - Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients

AU - Fraussen, Judith

AU - Vrolix, Kathleen

AU - Claes, Nele

AU - Martinez-Martinez, Pilar

AU - Losen, Mario

AU - Hupperts, Raymond

AU - Van Wijmeersch, Bart

AU - Espino, Mercedes

AU - Villar, Luisa M.

AU - De Baets, Marc H.

AU - Stinissen, Piet

AU - Somers, Veerle

PY - 2013/8/15

Y1 - 2013/8/15

N2 - We studied Ig heavy chain (VDJ) sequences and antigen reactivity of 412 immortalized B cell lines from the peripheral blood of 10 multiple sclerosis (MS) patients, 4 clinically isolated syndrome (CIS) patients and 6 healthy controls (HCs). 78/238 (32.8%) MS and CIS B cell lines were part of 9 clonally expanded B cell populations, of which 5 were present in multiple patients. Increased VH1 gene family usage was evidenced for MS B cells, with 29.2% expressing VH1-69. Affinity maturation in MS and CIS was indicated by increased Ig VDJ mutations. Autoantibody producing B cells reactive to intracellular antigens were significantly higher in MS (25%) and CIS (28%) patients than in HCs (5%), including 3/9 expanded B cell clones. Specificity for phosphatidylcholine was observed for 1/9 B cell clones. These findings indicate clonally expanded autoreactive B cells with affinity maturation in the peripheral blood in MS and CIS.

AB - We studied Ig heavy chain (VDJ) sequences and antigen reactivity of 412 immortalized B cell lines from the peripheral blood of 10 multiple sclerosis (MS) patients, 4 clinically isolated syndrome (CIS) patients and 6 healthy controls (HCs). 78/238 (32.8%) MS and CIS B cell lines were part of 9 clonally expanded B cell populations, of which 5 were present in multiple patients. Increased VH1 gene family usage was evidenced for MS B cells, with 29.2% expressing VH1-69. Affinity maturation in MS and CIS was indicated by increased Ig VDJ mutations. Autoantibody producing B cells reactive to intracellular antigens were significantly higher in MS (25%) and CIS (28%) patients than in HCs (5%), including 3/9 expanded B cell clones. Specificity for phosphatidylcholine was observed for 1/9 B cell clones. These findings indicate clonally expanded autoreactive B cells with affinity maturation in the peripheral blood in MS and CIS.

KW - Multiple sclerosis

KW - Clinically isolated syndrome

KW - B cell immortalization

KW - Complementarity determining region 3

KW - Clonal B cell expansion

KW - Autoreactivity

U2 - 10.1016/j.jneuroim.2013.05.002

DO - 10.1016/j.jneuroim.2013.05.002

M3 - Article

C2 - 23746373

VL - 261

SP - 98

EP - 107

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 1-2

ER -