Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires
Processes that define immunoglobulin repertoires are commonly presumed to be the same for all murine B cells. However, studies here that couple high-dimensional FACS sorting with large-scale quantitative IgH deep-sequencing demonstrate that B-1a IgH repertoire differs dramatically from the follicula...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2015-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/09083 |
| _version_ | 1818019110019137536 |
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| author | Yang Yang Chunlin Wang Qunying Yang Aaron B Kantor Hiutung Chu Eliver EB Ghosn Guang Qin Sarkis K Mazmanian Jian Han Leonore A Herzenberg |
| author_facet | Yang Yang Chunlin Wang Qunying Yang Aaron B Kantor Hiutung Chu Eliver EB Ghosn Guang Qin Sarkis K Mazmanian Jian Han Leonore A Herzenberg |
| author_sort | Yang Yang |
| collection | DOAJ |
| description | Processes that define immunoglobulin repertoires are commonly presumed to be the same for all murine B cells. However, studies here that couple high-dimensional FACS sorting with large-scale quantitative IgH deep-sequencing demonstrate that B-1a IgH repertoire differs dramatically from the follicular and marginal zone B cells repertoires and is defined by distinct mechanisms. We track B-1a cells from their early appearance in neonatal spleen to their long-term residence in adult peritoneum and spleen. We show that de novo B-1a IgH rearrangement mainly occurs during the first few weeks of life, after which their repertoire continues to evolve profoundly, including convergent selection of certain V(D)J rearrangements encoding specific CDR3 peptides in all adults and progressive introduction of hypermutation and class-switching as animals age. This V(D)J selection and AID-mediated diversification operate comparably in germ-free and conventional mice, indicating these unique B-1a repertoire-defining mechanisms are driven by antigens that are not derived from microbiota. |
| first_indexed | 2024-04-14T07:48:00Z |
| format | Article |
| id | doaj.art-84136b3938e744f4b65826e5869962c2 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:48:00Z |
| publishDate | 2015-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-84136b3938e744f4b65826e5869962c22022-12-22T02:05:17ZengeLife Sciences Publications LtdeLife2050-084X2015-09-01410.7554/eLife.09083Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoiresYang Yang0Chunlin Wang1Qunying Yang2Aaron B Kantor3Hiutung Chu4Eliver EB Ghosn5Guang Qin6Sarkis K Mazmanian7Jian Han8Leonore A Herzenberg9Genetics Department, Stanford University, Stanford, United StatesHudsonAlpha Institute for Biotechnology, Huntsville, United StatesHudsonAlpha Institute for Biotechnology, Huntsville, United StatesGenetics Department, Stanford University, Stanford, United StatesBiology and Biological Engineering Department, California Institute of Technology, Pasadena, United StatesGenetics Department, Stanford University, Stanford, United StatesGenetics Department, Stanford University, Stanford, United StatesBiology and Biological Engineering Department, California Institute of Technology, Pasadena, United StatesHudsonAlpha Institute for Biotechnology, Huntsville, United StatesGenetics Department, Stanford University, Stanford, United StatesProcesses that define immunoglobulin repertoires are commonly presumed to be the same for all murine B cells. However, studies here that couple high-dimensional FACS sorting with large-scale quantitative IgH deep-sequencing demonstrate that B-1a IgH repertoire differs dramatically from the follicular and marginal zone B cells repertoires and is defined by distinct mechanisms. We track B-1a cells from their early appearance in neonatal spleen to their long-term residence in adult peritoneum and spleen. We show that de novo B-1a IgH rearrangement mainly occurs during the first few weeks of life, after which their repertoire continues to evolve profoundly, including convergent selection of certain V(D)J rearrangements encoding specific CDR3 peptides in all adults and progressive introduction of hypermutation and class-switching as animals age. This V(D)J selection and AID-mediated diversification operate comparably in germ-free and conventional mice, indicating these unique B-1a repertoire-defining mechanisms are driven by antigens that are not derived from microbiota.https://elifesciences.org/articles/09083V(D)JdiversifyIgH |
| spellingShingle | Yang Yang Chunlin Wang Qunying Yang Aaron B Kantor Hiutung Chu Eliver EB Ghosn Guang Qin Sarkis K Mazmanian Jian Han Leonore A Herzenberg Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires eLife V(D)J diversify IgH |
| title | Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires |
| title_full | Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires |
| title_fullStr | Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires |
| title_full_unstemmed | Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires |
| title_short | Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires |
| title_sort | distinct mechanisms define murine b cell lineage immunoglobulin heavy chain igh repertoires |
| topic | V(D)J diversify IgH |
| url | https://elifesciences.org/articles/09083 |
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