Positive and negative selection shape the human naive B cell repertoire
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Although negative selection of developing B cells in the periphery is well described, yet poorly understood, evidence of naive B cell positive selection remains elusive. Using 2 humanized mouse models, we demonstrate that there was strong skewing of the expressed immunoglobulin repertoire upon transit into the peripheral naive B cell pool. This positive selection of expanded naive B cells in humanized mice resembled that observed in healthy human donors and was independent of autologous thymic tissue. In contrast, negative selection of autoreactive B cells required thymus-derived Tregs and MHC class II–restricted self-antigen presentation by B cells. Indeed, both defective MHC class II expression on B cells of patients with rare bare lymphocyte syndrome and prevention of self-antigen presentation via HLA-DM inhibition in humanized mice resulted in the production of autoreactive naive B cells. These latter observations suggest that Tregs repressed autoreactive naive B cells continuously produced by the bone marrow. Thus, a model emerged, in which both positive and negative selection shaped the human naive B cell repertoire and that each process was mediated by fundamentally different molecular and cellular mechanisms.
Details
Original language | English |
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Article number | 150985 |
Journal | Journal of Clinical Investigation |
Volume | 132 |
Issue number | 2 |
Publication status | Published - 18 Jan 2022 |
Peer-reviewed | Yes |
External IDs
PubMed | 34813502 |
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ORCID | /0009-0003-6519-0482/work/149439119 |