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

Authors :
Wong JB
Hewitt SL
Heltemes-Harris LM
Mandal M
Johnson K
Rajewsky K
Koralov SB
Clark MR
Farrar MA
Skok JA
Source :
Nature communications [Nat Commun] 2019 Oct 18; Vol. 10 (1), pp. 4768. Date of Electronic Publication: 2019 Oct 18.
Publication Year :
2019

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.

Details

Language :
English
ISSN :
2041-1723
Volume :
10
Issue :
1
Database :
MEDLINE
Journal :
Nature communications
Publication Type :
Academic Journal
Accession number :
31628339
Full Text :
https://doi.org/10.1038/s41467-019-12824-z