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

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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. and Hewitt, S.L. and Heltemes-Harris, L.M. and Mandal, M. and Johnson, K. and Rajewsky, K. and Koralov, S.B. and Clark, M.R. and 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:

Number:

Page Range:

4768

Date:

18 October 2019