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

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 predominantly 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 approximately 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.

• Authors: Gregory P Owens, Alanna M Ritchie, Mark P Burgoon, R Anthony Williamson, John R Corboy, Donald H Gilden
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 171 Issue 5 Pg. 2725-33 (Sep 01 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12928426 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD19
• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region
• Receptors, Antigen, B-Cell

Topics

• Acute Disease
• Adult
• Amino Acid Sequence
• Antigens, CD19 (biosynthesis)
• B-Lymphocyte Subsets (immunology, metabolism, pathology)
• Cell Separation
• Clone Cells
• Female
• Flow Cytometry
• Gene Rearrangement, B-Lymphocyte, Heavy Chain
• Gene Rearrangement, B-Lymphocyte, Light Chain
• Humans
• Immunoglobulin Heavy Chains (cerebrospinal fluid, genetics)
• Immunoglobulin Variable Region (cerebrospinal fluid, genetics)
• Lymphocyte Activation (genetics, immunology)
• Male
• Meningitis, Viral (cerebrospinal fluid, genetics, immunology)
• Middle Aged
• Molecular Sequence Data
• Multiple Sclerosis (cerebrospinal fluid, genetics, immunology)
• Receptors, Antigen, B-Cell (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction