Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 183, Issue 1-2, Pages 189-199Publisher
ELSEVIER
DOI: 10.1016/j.jneuroim.2006.10.020
Keywords
multiple Sclerosis; cerebrospinal fluid; B lymphocytes; immunoglobulin rearrangements; mutation accumulation
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Funding
- NIAID NIH HHS [T32 AI005284, T32 AI 005284-28, R01 AI 47133] Funding Source: Medline
- NINDS NIH HHS [K24 NS 44250, R01 NS 37513, R01 NS040993, K24 NS044250, R01 NS 40993, R01 NS037513] Funding Source: Medline
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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. (c) 2006 Elsevier B.V. All rights reserved.
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