TY - JOUR
T1 - Cerebrospinal fluid B cells from multiple sclerosis patients are subject to normal germinal center selection
AU - Harp, Christopher
AU - Lee, Jane
AU - Washington, Doris L
AU - Cameron, Elizabeth
AU - Olsen, Gregory
AU - Frohman, Elliot
AU - Racke, Michael
AU - Monson, Nancy L
PY - 2007/2
Y1 - 2007/2
N2 - Previous findings from our laboratory demonstrated that some clonally expanded cerebrospinal fluid (CSF) B cells from MS patients exhibit diminished mutation targeting patterns in comparison to typical B cells selected in the context of germinal centers (GCs). In order to determine whether the overall CSF B cell repertoires adhered to mutation patterns typical of GC-selected B cells, we analyzed the immunoglobulin repertoires from CSF B cells of 8 MS patients for mutation characteristics typical of GC-derived B cells. Mutation targeting was preserved. Thus, clonal expansion of some CSF B cells may occur independently of GC, but the CSF B cell pool is governed by typical GC selection. Interestingly, the heavy chain CDR3's of CSF B cells from MS patients had a net acidic charge, similar to GC-derived B cells, but a tendency towards longer CDR3's, consistent with autoreactive B cells. How these findings may support current hypotheses regarding the origin of CSF B cells is discussed.
AB - Previous findings from our laboratory demonstrated that some clonally expanded cerebrospinal fluid (CSF) B cells from MS patients exhibit diminished mutation targeting patterns in comparison to typical B cells selected in the context of germinal centers (GCs). In order to determine whether the overall CSF B cell repertoires adhered to mutation patterns typical of GC-selected B cells, we analyzed the immunoglobulin repertoires from CSF B cells of 8 MS patients for mutation characteristics typical of GC-derived B cells. Mutation targeting was preserved. Thus, clonal expansion of some CSF B cells may occur independently of GC, but the CSF B cell pool is governed by typical GC selection. Interestingly, the heavy chain CDR3's of CSF B cells from MS patients had a net acidic charge, similar to GC-derived B cells, but a tendency towards longer CDR3's, consistent with autoreactive B cells. How these findings may support current hypotheses regarding the origin of CSF B cells is discussed.
KW - B lymphocytes
KW - Cerebrospinal fluid
KW - Immunoglobulin rearrangements
KW - Multiple Sclerosis
KW - Mutation accumulation
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U2 - 10.1016/j.jneuroim.2006.10.020
DO - 10.1016/j.jneuroim.2006.10.020
M3 - Article
C2 - 17169437
AN - SCOPUS:33846846443
SN - 0165-5728
VL - 183
SP - 189
EP - 199
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -