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 and Jane A. Skok ()
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Jason B. Wong: New York University School of Medicine, New York University
Susannah L. Hewitt: New York University School of Medicine, New York University
Lynn M. Heltemes-Harris: University of Minnesota
Malay Mandal: University of Chicago
Kristen Johnson: New York University School of Medicine, New York University
Klaus Rajewsky: Max Delbrück Center for Molecular Medicine
Sergei B. Koralov: New York University School of Medicine, New York University
Marcus R. Clark: University of Chicago
Michael A. Farrar: University of Minnesota
Jane A. Skok: New York University School of Medicine, New York University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12824-z

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