4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12824-z

Keywords

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Funding

  1. Cancer Center Support Grant at the Laura and Isaac Perlmutter Cancer Cenert [P30CA016087]
  2. NIH [R35GM122515, CA151845, CA154998]
  3. American Society of Hematology (ASH) Scholar Award
  4. Molecular Oncology and Immunology Training Grant NIH T32
  5. [T32 CA009161]
  6. [2T32 AI100853-06]

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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.

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