A Single Human VH-gene Allows for a Broad-Spectrum Antibody Response Targeting Bacterial Lipopolysaccharides in the Blood
Summary: B cell receptors (BCRs) display a combination of variable (V)-gene-encoded complementarity determining regions (CDRs) and adaptive/hypervariable CDR3 loops to engage antigens. It has long been proposed that the former tune for recognition of pathogens or groups of pathogens. To experimental...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720310500 |
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doaj-4869d22e49344399b1979bd3c854bad0 |
|---|---|
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Maya Sangesland Ashraf S. Yousif Larance Ronsard Samuel W. Kazer Alex Lee Zhu G. James Gatter Matthew R. Hayward Ralston M. Barnes Maricel Quirindongo-Crespo Daniel Rohrer Nils Lonberg Douglas Kwon Alex K. Shalek Daniel Lingwood |
| spellingShingle |
Maya Sangesland Ashraf S. Yousif Larance Ronsard Samuel W. Kazer Alex Lee Zhu G. James Gatter Matthew R. Hayward Ralston M. Barnes Maricel Quirindongo-Crespo Daniel Rohrer Nils Lonberg Douglas Kwon Alex K. Shalek Daniel Lingwood A Single Human VH-gene Allows for a Broad-Spectrum Antibody Response Targeting Bacterial Lipopolysaccharides in the Blood Cell Reports BCR germline VH pattern-recognition bacteria antiseptic |
| author_facet |
Maya Sangesland Ashraf S. Yousif Larance Ronsard Samuel W. Kazer Alex Lee Zhu G. James Gatter Matthew R. Hayward Ralston M. Barnes Maricel Quirindongo-Crespo Daniel Rohrer Nils Lonberg Douglas Kwon Alex K. Shalek Daniel Lingwood |
| author_sort |
Maya Sangesland |
| title |
A Single Human VH-gene Allows for a Broad-Spectrum Antibody Response Targeting Bacterial Lipopolysaccharides in the Blood |
| title_short |
A Single Human VH-gene Allows for a Broad-Spectrum Antibody Response Targeting Bacterial Lipopolysaccharides in the Blood |
| title_full |
A Single Human VH-gene Allows for a Broad-Spectrum Antibody Response Targeting Bacterial Lipopolysaccharides in the Blood |
| title_fullStr |
A Single Human VH-gene Allows for a Broad-Spectrum Antibody Response Targeting Bacterial Lipopolysaccharides in the Blood |
| title_full_unstemmed |
A Single Human VH-gene Allows for a Broad-Spectrum Antibody Response Targeting Bacterial Lipopolysaccharides in the Blood |
| title_sort |
single human vh-gene allows for a broad-spectrum antibody response targeting bacterial lipopolysaccharides in the blood |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-08-01 |
| description |
Summary: B cell receptors (BCRs) display a combination of variable (V)-gene-encoded complementarity determining regions (CDRs) and adaptive/hypervariable CDR3 loops to engage antigens. It has long been proposed that the former tune for recognition of pathogens or groups of pathogens. To experimentally evaluate this within the human antibody repertoire, we perform immune challenges in transgenic mice that bear diverse human CDR3 and light chains but are constrained to different human VH-genes. We find that, of six commonly deployed VH sequences, only those CDRs encoded by IGHV1-2∗02 enable polyclonal antibody responses against bacterial lipopolysaccharide (LPS) when introduced to the bloodstream. The LPS is from diverse strains of gram-negative bacteria, and the VH-gene-dependent responses are directed against the non-variable and universal saccrolipid substructure of this antigen. This reveals a broad-spectrum anti-LPS response in which germline-encoded CDRs naturally hardwire the human antibody repertoire for recognition of a conserved microbial target. |
| topic |
BCR germline VH pattern-recognition bacteria antiseptic |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124720310500 |
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1724525350779617280 |
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doaj-4869d22e49344399b1979bd3c854bad02020-11-25T03:42:24ZengElsevierCell Reports2211-12472020-08-01328108065A Single Human VH-gene Allows for a Broad-Spectrum Antibody Response Targeting Bacterial Lipopolysaccharides in the BloodMaya Sangesland0Ashraf S. Yousif1Larance Ronsard2Samuel W. Kazer3Alex Lee Zhu4G. James Gatter5Matthew R. Hayward6Ralston M. Barnes7Maricel Quirindongo-Crespo8Daniel Rohrer9Nils Lonberg10Douglas Kwon11Alex K. Shalek12Daniel Lingwood13The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science (IMES), Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main St., Cambridge, MA 02142, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science (IMES), Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main St., Cambridge, MA 02142, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USABristol-Myers Squibb, 700 Bay Rd., Redwood City, CA 94063-2478, USABristol-Myers Squibb, 700 Bay Rd., Redwood City, CA 94063-2478, USABroad Institute of Massachusetts Institute of Technology and Harvard, 415 Main St., Cambridge, MA 02142, USABristol-Myers Squibb, 700 Bay Rd., Redwood City, CA 94063-2478, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Division of Infectious Diseases, Massachusetts General Hospital. 55 Fruit St., Boston, MA 02114, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science (IMES), Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main St., Cambridge, MA 02142, USAThe Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA; Corresponding authorSummary: B cell receptors (BCRs) display a combination of variable (V)-gene-encoded complementarity determining regions (CDRs) and adaptive/hypervariable CDR3 loops to engage antigens. It has long been proposed that the former tune for recognition of pathogens or groups of pathogens. To experimentally evaluate this within the human antibody repertoire, we perform immune challenges in transgenic mice that bear diverse human CDR3 and light chains but are constrained to different human VH-genes. We find that, of six commonly deployed VH sequences, only those CDRs encoded by IGHV1-2∗02 enable polyclonal antibody responses against bacterial lipopolysaccharide (LPS) when introduced to the bloodstream. The LPS is from diverse strains of gram-negative bacteria, and the VH-gene-dependent responses are directed against the non-variable and universal saccrolipid substructure of this antigen. This reveals a broad-spectrum anti-LPS response in which germline-encoded CDRs naturally hardwire the human antibody repertoire for recognition of a conserved microbial target.http://www.sciencedirect.com/science/article/pii/S2211124720310500BCRgermlineVHpattern-recognitionbacteriaantiseptic |