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B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage.
- 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.
- Subjects :
- Animals
B-Lymphocyte Subsets metabolism
B-Lymphocytes metabolism
Bone Marrow immunology
Bone Marrow metabolism
Cell Differentiation genetics
Immunoglobulin Light Chains, Surrogate genetics
Immunoglobulin Light Chains, Surrogate immunology
Immunoglobulin Light Chains, Surrogate metabolism
Liver embryology
Liver immunology
Liver metabolism
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Mice, Inbred C57BL
Mice, Knockout
Pre-B Cell Receptors genetics
Pre-B Cell Receptors metabolism
Receptors, Antigen, B-Cell genetics
Receptors, Antigen, B-Cell metabolism
Receptors, Interleukin-7 genetics
Receptors, Interleukin-7 immunology
Receptors, Interleukin-7 metabolism
STAT5 Transcription Factor genetics
STAT5 Transcription Factor immunology
STAT5 Transcription Factor metabolism
B-Lymphocyte Subsets immunology
B-Lymphocytes immunology
Cell Differentiation immunology
Pre-B Cell Receptors immunology
Receptors, Antigen, B-Cell immunology
Subjects
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