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

Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2743-8. doi: 10.1073/pnas.050552997.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology*
  • Cell Death
  • Cell Differentiation
  • Cloning, Molecular
  • Flow Cytometry
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Light Chains / immunology
  • Immunoglobulin M / immunology
  • Immunologic Memory
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Receptors, Antigen, B-Cell / physiology*
  • Spleen / cytology
  • Stochastic Processes

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin M
  • Receptors, Antigen, B-Cell

Associated data

  • GENBANK/AF076238