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The Journal of Immunology, 2003, 171: 2725-2733.
Copyright © 2003 by The American Association of Immunologists

Single-Cell Repertoire Analysis Demonstrates that Clonal Expansion Is a Prominent Feature of the B Cell Response in Multiple Sclerosis Cerebrospinal Fluid 1

Gregory P. Owens2,*, Alanna M. Ritchie*, Mark P. Burgoon*, R. Anthony Williamson{ddagger}, John R. Corboy* and Donald H. Gilden*,{dagger}

Departments of * Neurology and {dagger} Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262; and {ddagger} Department of Immunology, Scripps Research Institute, La Jolla, CA 92037

Single-cell RT-PCR was used to sample CD19+ B cell repertoires in cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) or viral meningitis. Analysis of amplified Ab H and L chain products served to identify the rearranged germline segment and J segment, and to determine the degree of homology for the H and L chain sequence of individual B cells. The B cell repertoire of viral meningitis CSF was predominately polyclonal, whereas B cell clonal expansion was a prominent feature of the IgG repertoire in three of four MS patients. Two dominant clonal populations in one MS CSF accounted for ~70% of the IgG H chain V regions sequenced, while the corresponding IgM repertoires were more heterogeneous. One clonal B cell population revealed multiple L chain rearrangements, raising the possibility of a role for receptor editing in shaping the B cell response in some MS patients. The most immediate implications of identifying rearranged Ig sequences in MS B cells is the potential to accurately recreate recombinant Abs from these overrepresented H and L chains that can be used to discover the relevant Ag(s) in MS.




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