Evidence of marginal-zone B cell-positive selection in spleen

Immunity. 2005 Sep;23(3):297-308. doi: 10.1016/j.immuni.2005.08.007.

Abstract

Antigen receptor-mediated signaling is critical for the development and survival of B cells. However, it has not been established whether B cell development requires a signal from self-ligand engagement at the immature stage, a process known as "positive selection." Here, using a monoclonal B cell receptor (BCR) mouse line, specific for the self-Thy-1/CD90 glycoprotein, we demonstrate that BCR crosslinking by low-dose self-antigen promotes survival of immature B cells in culture. In spleen, an increase in BCR signaling strength, induced by low-dose self-antigen, directed naive immature B cells to mature, not into the default follicular B cell fate, but instead into the marginal-zone B cell subset. These data indicate that positive selection can occur in developing B cells and that BCR signal strength is a key factor in deciding between two functionally distinct mature B cell compartments in the microenvironment of the spleen.

Publication types

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

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Line
  • Clonal Deletion / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Mice
  • Mice, Transgenic
  • Receptor, Notch2
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Spleen / cytology
  • Spleen / immunology*
  • Thy-1 Antigens / immunology

Substances

  • Autoantibodies
  • Autoantigens
  • Notch2 protein, mouse
  • Receptor, Notch2
  • Receptors, Antigen, B-Cell
  • Receptors, Cell Surface
  • Thy-1 Antigens