Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis.
We describe a method for correlating the immunoglobulin (Ig) proteomes with the B cell transcriptomes in human fluid and tissue samples, using multiple sclerosis as a paradigm. Oligoclonal Ig bands and elevated numbers of clonally expanded B cells in the cerebrospinal fluid (CSF) are diagnostic hallmarks of multiple sclerosis. Here we compared the Ig transcriptomes of B cells with the corresponding Ig proteomes in CSF samples from four subjects with multiple sclerosis. We created individual Ig transcriptome databases that contained the subject-specific mutations introduced by V(D)J recombination and somatic hypermutation and then searched the CSF for corresponding characteristic peptides by mass spectrometry. In each sample, the Ig transcriptomes and proteomes strongly overlapped, showing that CSF B cells indeed produce the oligoclonal Ig bands. This approach can be applied to other organ-specific diagnostic fluid or tissue samples to compare the Ig transcripts of local B cells with the corresponding antibody proteomes of individual subjects.
Obermeier
Birgit
B
Institute of Clinical Neuroimmunology, Ludwig Maximilians University, University Hospital Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany.
Mentele
Reinhard
R
Malotka
Joachim
J
Kellermann
Josef
J
Kümpfel
Tania
T
Wekerle
Hartmut
H
Lottspeich
Friedrich
F
Hohlfeld
Reinhard
R
Dornmair
Klaus
K
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D002556:Cerebrospinal Fluid Proteins / Q000235:genetics / Q000276:immunology*; D030541:Databases, Genetic; D005782:Gels; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007525:Isoelectric Focusing; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology; D043025:Oligoclonal Bands / Q000235:genetics* / Q000276:immunology; D020543:Proteome / Q000032:analysis*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D002556:Cerebrospinal Fluid Proteins; D005782:Gels; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D043025:Oligoclonal Bands; D020543:Proteome