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| Item Type: | Article |
|---|---|
| Title: | B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage |
| Creators Name: | Wong, J.B., Hewitt, S.L., Heltemes-Harris, L.M., Mandal, M., Johnson, K., Rajewsky, K., Koralov, S.B., Clark, M.R., Farrar, M.A. and Skok, J.A. |
| Abstract: | B-1a cells are long-lived, self-renewing innate-like B cells that predominantly inhabit the peritoneal and pleural cavities. In contrast to conventional B-2 cells, B-1a cells have a receptor repertoire that is biased towards bacterial and self-antigens, promoting a rapid response to infection and clearing of apoptotic cells. Although B-1a cells are known to primarily originate from fetal tissues, the mechanisms by which they arise has been a topic of debate for many years. Here we show that in the fetal liver versus bone marrow environment, reduced IL-7R/STAT5 levels promote immunoglobulin kappa gene recombination at the early pro-B cell stage. As a result, differentiating B cells can directly generate a mature B cell receptor (BCR) and bypass the requirement for a pre-BCR and pairing with surrogate light chain. This 'alternate pathway' of development enables the production of B cells with self-reactive, skewed specificity receptors that are peculiar to the B-1a compartment. Together our findings connect seemingly opposing lineage and selection models of B-1a cell development and explain how these cells acquire their unique properties. |
| Keywords: | B-Cell Antigen Receptors, B-Lymphocyte Subsets, B-Lymphocytes, Bone Marrow, Cell Differentiation, Inbred C57BL Mice, Interleukin-7 Receptors, Knockout Mice, Liver, Lymphocyte Activation, Pre-B Cell Receptors, STAT5 Transcription Factor, Surrogate Immunoglobulin Light Chains, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 10 |
| Number: | 1 |
| Page Range: | 4768 |
| Date: | 18 October 2019 |
| Official Publication: | https://doi.org/10.1038/s41467-019-12824-z |
| PubMed: | View item in PubMed |
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