B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage

Jason B. Wong, Susannah L. Hewitt, Lynn M. Heltemes-Harris, Malay Mandal, Kristen Johnson, Klaus Rajewsky, Sergei B. Koralov, Marcus R. Clark, Michael A. Farrar, Jane A. Skok

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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.

Original languageEnglish (US)
Article number4768
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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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., & Skok, J. A. (2019). B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage. Nature communications, 10(1), [4768]. https://doi.org/10.1038/s41467-019-12824-z