Abstract
Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material. Gene expression profiling and real time PCR detected however no CD8A or CD8B message in these cells. Instead, we found that surface CD8 was hijacked from activated CD8+ T cells by a transfer process that required direct cell-to-cell contact. A focused transcriptome analysis at single cell level allowed the dissection of the CD8 positive B cell population. We found that the affected cells are characteristically of the CD27+CD200- phenotype, and consist of two discrete late-stage subpopulations that carry signatures of activated memory B like cells, and early plasmablasts. Thus, there is only a restricted time window in the differentiation process during which B cells can intimately interact with CD8+ T cells. The findings point to a novel link between the T and B arms of the adaptive immune system, and suggest that CD8+ T cells have the capability to directly shape the global antibody repertoire.
MeSH terms
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Antigens, CD / genetics
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Antigens, CD / metabolism
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism
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CD8 Antigens / genetics
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CD8 Antigens / immunology
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CD8 Antigens / metabolism*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / microbiology*
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Cell Communication / immunology*
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Cell Differentiation / immunology
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Cell Separation
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Cells, Cultured
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Flow Cytometry
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Gene Expression Profiling
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Healthy Volunteers
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Humans
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Immunologic Memory*
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Primary Cell Culture
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RNA, Messenger / analysis
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Single-Cell Analysis
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
Substances
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Antigens, CD
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CD8 Antigens
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CD8 antigen, alpha chain
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CD8alphabeta antigen
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CD8beta antigen
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RNA, Messenger
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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antigens, CD200
Grants and funding
The authors are employees of Novartis and received no specific funding for this work. Novartis provided support in the form of salaries for all authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.