Single-cell repertoire analysis demonstrates that clonal expansion is a prominent feature of the B cell response in multiple sclerosis cerebrospinal fluid

GP Owens, AM Ritchie, MP Burgoon… - The Journal of …, 2003 - journals.aai.org
GP Owens, AM Ritchie, MP Burgoon, RA Williamson, JR Corboy, DH Gilden
The Journal of Immunology, 2003journals.aai.org
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 …
Abstract
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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