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A B-cell receptor-specific selection step governs immature to mature B cell differentiation.


ABSTRACT: Seventy percent of peripheral immature conventional (B2) B cells fail to develop into mature B cells. The nature of this cell loss has not been characterized; the process that governs which immature B cells develop into long-lived peripheral B cells could be either stochastic or selective. Here, we demonstrate that this step is in fact selective, in that the fate of an immature B cell is highly dependent on its Ig receptor specificity. A significant skewing of the B cell receptor repertoire occurs by the time cells enter the mature B cell fraction, which indicates that there is selection of only a minority of immature B cells to become mature B cells. Because only a few heavy-light chain pairs are enhanced of the diverse available repertoire, we favor the idea that selection is positive for these few heavy-light chain pairs rather than negative against nearly all others. Because most immature B cells are lost at this transition, this putative positive selection event is likely to be a major force shaping the mature B cell receptor repertoire available for adaptive immune responses.

SUBMITTER: Levine MH 

PROVIDER: S-EPMC16000 | biostudies-literature | 2000 Mar

REPOSITORIES: biostudies-literature

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A B-cell receptor-specific selection step governs immature to mature B cell differentiation.

Levine M H MH   Haberman A M AM   Sant'Angelo D B DB   Hannum L G LG   Cancro M P MP   Janeway C A CA   Shlomchik M J MJ  

Proceedings of the National Academy of Sciences of the United States of America 20000301 6


Seventy percent of peripheral immature conventional (B2) B cells fail to develop into mature B cells. The nature of this cell loss has not been characterized; the process that governs which immature B cells develop into long-lived peripheral B cells could be either stochastic or selective. Here, we demonstrate that this step is in fact selective, in that the fate of an immature B cell is highly dependent on its Ig receptor specificity. A significant skewing of the B cell receptor repertoire occu  ...[more]

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