Antigen specificity of clonally expanded and receptor edited cerebrospinal fluid B cells from patients with relapsing remitting MS.
We re-engineered the immunoglobulin rearrangements from clonally expanded CSF B cells of three Multiple Sclerosis patients as Fab fragments, and used three methods to test for their antigen (Ag) specificity. Nine out of ten Fab fragments were reactive to Myelin Basic Protein (MBP). The one Fab that did not react to MBP was a product of receptor editing. Two of the nine MBP reactive Fabs were also reactive to GFAP and CNPase, indicating that these clones were polyreactive. Targeting the mechanisms that allow these self-reactive B cells to reside in the CSF of MS patients may prove to be a potent immunotherapeutic strategy.
Lambracht-Washington
Doris
D
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
O'Connor
Kevin C
KC
Cameron
Elizabeth M
EM
Jowdry
Andrea
A
Ward
E Sally
ES
Frohman
Elliot
E
Racke
Michael K
MK
Monson
Nancy L
NL
D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte / Q000502:physiology; D005803:Genes, Immunoglobulin; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000378:metabolism; D047468:Immunoprecipitation; D018448:Models, Immunological; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*
D001324:Autoantigens; D005904:Glial Fibrillary Acidic Protein; D007140:Immunoglobulin Fab Fragments; D004676:Myelin Basic Protein