Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigens
Abstract Several lines of evidence indirectly suggest that antigenic stimulation through the B‐cell receptor (BCR) supports chronic lymphocytic leukemia (CLL) development. In addition to self‐antigens, a number of microbial antigens have been proposed to contribute to the selection of the immunoglob...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-09-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201707732 |
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| author | Nereida Jiménez de Oya Marco De Giovanni Jessica Fioravanti Rudolf Übelhart Pietro Di Lucia Amleto Fiocchi Stefano Iacovelli Dimitar G Efremov Federico Caligaris‐Cappio Hassan Jumaa Paolo Ghia Luca G Guidotti Matteo Iannacone |
| author_facet | Nereida Jiménez de Oya Marco De Giovanni Jessica Fioravanti Rudolf Übelhart Pietro Di Lucia Amleto Fiocchi Stefano Iacovelli Dimitar G Efremov Federico Caligaris‐Cappio Hassan Jumaa Paolo Ghia Luca G Guidotti Matteo Iannacone |
| author_sort | Nereida Jiménez de Oya |
| collection | DOAJ |
| description | Abstract Several lines of evidence indirectly suggest that antigenic stimulation through the B‐cell receptor (BCR) supports chronic lymphocytic leukemia (CLL) development. In addition to self‐antigens, a number of microbial antigens have been proposed to contribute to the selection of the immunoglobulins expressed in CLL. How pathogen‐specific BCRs drive CLL development remains, however, largely unexplored. Here, we utilized mouse models of CLL pathogenesis to equip B cells with virus‐specific BCRs and study the effect of antigen recognition on leukemia growth. Our results show that BCR engagement is absolutely required for CLL development. Unexpectedly, however, neither acute nor chronic exposure to virus‐derived antigens influenced leukemia progression. Rather, CLL clones preferentially selected light chains that, when paired with virus‐specific heavy chains, conferred B cells the ability to recognize a broad range of autoantigens. Taken together, our results suggest that pathogens may drive CLL pathogenesis by selecting and expanding pathogen‐specific B cells that cross‐react with one or more self‐antigens. |
| format | Article |
| id | doaj-art-bd9fe90f9288488ea8972d0c1f258c6d |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2017-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-bd9fe90f9288488ea8972d0c1f258c6d2025-08-20T03:46:21ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-09-019111482149010.15252/emmm.201707732Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigensNereida Jiménez de Oya0Marco De Giovanni1Jessica Fioravanti2Rudolf Übelhart3Pietro Di Lucia4Amleto Fiocchi5Stefano Iacovelli6Dimitar G Efremov7Federico Caligaris‐Cappio8Hassan Jumaa9Paolo Ghia10Luca G Guidotti11Matteo Iannacone12Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific InstituteDivision of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific InstituteDivision of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific InstituteInstitute of Immunology, University Hospital UlmDivision of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific InstituteDivision of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific InstituteMolecular Hematology Unit, International Centre for Genetic Engineering & BiotechnologyMolecular Hematology Unit, International Centre for Genetic Engineering & BiotechnologyDivision of Experimental Oncology, IRCCS San Raffaele Scientific InstituteInstitute of Immunology, University Hospital UlmVita‐Salute San Raffaele UniversityDivision of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific InstituteDivision of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific InstituteAbstract Several lines of evidence indirectly suggest that antigenic stimulation through the B‐cell receptor (BCR) supports chronic lymphocytic leukemia (CLL) development. In addition to self‐antigens, a number of microbial antigens have been proposed to contribute to the selection of the immunoglobulins expressed in CLL. How pathogen‐specific BCRs drive CLL development remains, however, largely unexplored. Here, we utilized mouse models of CLL pathogenesis to equip B cells with virus‐specific BCRs and study the effect of antigen recognition on leukemia growth. Our results show that BCR engagement is absolutely required for CLL development. Unexpectedly, however, neither acute nor chronic exposure to virus‐derived antigens influenced leukemia progression. Rather, CLL clones preferentially selected light chains that, when paired with virus‐specific heavy chains, conferred B cells the ability to recognize a broad range of autoantigens. Taken together, our results suggest that pathogens may drive CLL pathogenesis by selecting and expanding pathogen‐specific B cells that cross‐react with one or more self‐antigens.https://doi.org/10.15252/emmm.201707732autoantigensB‐cell receptorchronic lymphocytic leukemiainfectionlight chains |
| spellingShingle | Nereida Jiménez de Oya Marco De Giovanni Jessica Fioravanti Rudolf Übelhart Pietro Di Lucia Amleto Fiocchi Stefano Iacovelli Dimitar G Efremov Federico Caligaris‐Cappio Hassan Jumaa Paolo Ghia Luca G Guidotti Matteo Iannacone Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigens EMBO Molecular Medicine autoantigens B‐cell receptor chronic lymphocytic leukemia infection light chains |
| title | Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigens |
| title_full | Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigens |
| title_fullStr | Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigens |
| title_full_unstemmed | Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigens |
| title_short | Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigens |
| title_sort | pathogen specific b cell receptors drive chronic lymphocytic leukemia by light chain dependent cross reaction with autoantigens |
| topic | autoantigens B‐cell receptor chronic lymphocytic leukemia infection light chains |
| url | https://doi.org/10.15252/emmm.201707732 |
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