Cerebrospinal fluid B cells from multiple sclerosis patients are subject to normal germinal center selection.
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.
Harp
Christopher
C
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lee
Jane
J
Lambracht-Washington
Doris
D
Cameron
Elizabeth
E
Olsen
Gregory
G
Frohman
Elliot
E
Racke
Michael
M
Monson
Nancy
N
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D005803:Genes, Immunoglobulin / Q000235:genetics; D018858:Germinal Center / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D018709:Statistics, Nonparametric
D011947:Receptors, Antigen, B-Cell