A checkpoint for autoreactivity in human IgM+ memory B cell development Journal Article
| Authors: | Tsuiji, M.; Yurasov, S.; Velinzon, K.; Thomas, S.; Nussenzweig, M. C.; Wardemann, H. |
| Article Title: | A checkpoint for autoreactivity in human IgM+ memory B cell development |
| Abstract: | Autoantibodies are removed from the repertoire at two checkpoints during B cell development in the bone marrow and the periphery. Despite these checkpoints, up to 20% of the antibodies expressed by mature naive B cells in healthy humans show low levels of self-reactivity. To determine whether self-reactive antibodies are also part of the antigen-experienced memory B cell compartment, we analyzed recombinant antibodies cloned from single circulating human IgM+ memory B cells. Cells expressing antibodies specific for individual bacterial polysaccharides were expanded in the IgM+ memory compartment. In contrast, B cells expressing self-reactive and broadly bacterially reactive antibodies were removed from the repertoire in the transition from naive to IgM+ memory B cell. Selection against self-reactive antibodies was implemented before the onset of somatic hypermutation. We conclude that a third checkpoint selects against self-reactivity during IgM+ memory B cell development in humans. JEM © The Rockefeller University Press. |
| Keywords: | controlled study; protein expression; human cell; somatic mutation; cells, cultured; cell compartmentalization; cell maturation; cell differentiation; immunoreactivity; b lymphocyte; b-lymphocytes; molecular cloning; immunoglobulin variable region; immunoglobulin heavy chains; antigen; recombinant antibody; antibody specificity; autoantibody; memory cell; autoantibodies; immunologic memory; antibody production; normal human; immunoglobulin m; g0 phase; antigens, bacterial; polysaccharides, bacterial; bacterium lipopolysaccharide; staphylococcal protein a |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 203 |
| Issue: | 2 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2006-02-20 |
| Start Page: | 393 |
| End Page: | 400 |
| Language: | English |
| DOI: | 10.1084/jem.20052033 |
| PUBMED: | 16446381 |
| PROVIDER: | scopus |
| PMCID: | PMC2118214 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 81" - "Export Date: 4 June 2012" - "CODEN: JEMEA" - "Source: Scopus" |
