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Peptide reactivity between multiple sclerosis (MS) CSF IgG and recombinant antibodies generated from clonally expanded plasma cells in MS CSF.

ABSTRACT: We employed 19 recombinant antibodies (rAbs) generated from clonally expanded plasma cells, and native IgG from cerebrospinal fluid (CSF) of three multiple sclerosis (MS) patients for panning with phage displayed random peptide libraries. Specific peptide epitopes/mimotopes were identified and characterized. Importantly, peptide-antibody interactions were shared by rAbs and native IgG from the same patient. Three peptides strongly interacted with at least one other MS CSF, but not to inflammatory CNS controls. Database searches revealed several protein candidates including stress proteins, cell surface proteins, and neuronal proteins. Peptides derived from the candidate proteins were recognized by rAbs. Identification of peptide epitopes/mimotopes in MS may provide clues regarding disease-relevant antigens.

SUBMITTER: Yu X

PROVIDER: S-EPMC3277395 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Peptide reactivity between multiple sclerosis (MS) CSF IgG and recombinant antibodies generated from clonally expanded plasma cells in MS CSF.

Yu Xiaoli X Gilden Don D Schambers Laura L Barmina Olga O Burgoon Mark M Bennett Jeffrey J Owens Greg G

Journal of neuroimmunology 20101221 1-2

We employed 19 recombinant antibodies (rAbs) generated from clonally expanded plasma cells, and native IgG from cerebrospinal fluid (CSF) of three multiple sclerosis (MS) patients for panning with phage displayed random peptide libraries. Specific peptide epitopes/mimotopes were identified and characterized. Importantly, peptide-antibody interactions were shared by rAbs and native IgG from the same patient. Three peptides strongly interacted with at least one other MS CSF, but not to inflammator ...[more]

PMID: 21176973

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Project description:In breast cancer, humoral immune responses may contribute to clinical outcomes, especially in more immunogenic subtypes. Here, we investigated B lymphocyte subsets, immunoglobulin expression, and clonal features in breast tumors, focusing on aggressive triple-negative breast cancers (TNBC). In samples from patients with TNBC and healthy volunteers, circulating and tumor-infiltrating B lymphocytes (TIL-B) were evaluated. CD20+CD27+IgD- isotype-switched B lymphocytes were increased in tumors, compared with matched blood. TIL-B frequently formed stromal clusters with T lymphocytes and engaged in bidirectional functional cross-talk, consistent with gene signatures associated with lymphoid assembly, costimulation, cytokine-cytokine receptor interactions, cytotoxic T-cell activation, and T-cell-dependent B-cell activation. TIL-B-upregulated B-cell receptor (BCR) pathway molecules FOS and JUN, germinal center chemokine regulator RGS1, activation marker CD69, and TNFα signal transduction via NFκB, suggesting BCR-immune complex formation. Expression of genes associated with B lymphocyte recruitment and lymphoid assembly, including CXCL13, CXCR4, and DC-LAMP, was elevated in TNBC compared with other subtypes and normal breast. TIL-B-rich tumors showed expansion of IgG but not IgA isotypes, and IgG isotype switching positively associated with survival outcomes in TNBC. Clonal expansion was biased toward IgG, showing expansive clonal families with specific variable region gene combinations and narrow repertoires. Stronger positive selection pressure was present in the complementarity determining regions of IgG compared with their clonally related IgA in tumor samples. Overall, class-switched B lymphocyte lineage traits were conspicuous in TNBC, associated with improved clinical outcomes, and conferred IgG-biased, clonally expanded, and likely antigen-driven humoral responses. SIGNIFICANCE: Tumor-infiltrating B lymphocytes assemble in clusters, undergoing B-cell receptor-driven activation, proliferation, and isotype switching. Clonally expanded, IgG isotype-biased humoral immunity associates with favorable prognosis primarily in triple-negative breast cancers.

Dataset Information

Peptide reactivity between multiple sclerosis (MS) CSF IgG and recombinant antibodies generated from clonally expanded plasma cells in MS CSF.

Publications

Peptide reactivity between multiple sclerosis (MS) CSF IgG and recombinant antibodies generated from clonally expanded plasma cells in MS CSF.

Similar Datasets

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