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
SN - 0165-5728
VL - 261
SP - 98
EP - 107
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -